To a woman nine-months pregnant, an intravenous drip of synthetic oxytocin is a powerful elixir. The drug most commonly used to induce labor in the U.S., oxytocin is also a natural hormone made in the hypothalamus and released into the bloodstream by the posterior pituitary gland. During labor, oxytocin stimulates the uterine muscle to contract. A long-pregnant woman's uterus responds so strongly and readily to both the natural and synthetic versions because she has more oxytocin receptors at childbirth than at any other time in her life. By the time she gives birth, oxytocin receptors in her uterus have climbed to 300-fold their normal levels.
Oxytocin was discovered in 1909 when Sir Henry H. Dale found that an extract from the human posterior pituitary gland contracted the uterus of a pregnant cat. (The hormone is found unchanged in every mammalian species.) Dale named the unknown substance oxytocin, using the Greek words for "quick" and "birth." As early as 1911, physicians began using the pituitary extract to stimulate childbirth contractions. Dale subsequently found that the same extract facilitates the release of mother's milk. Oxytocin contracts the smooth-muscle cells surrounding the mammary glands to move milk into the nipple--called milk "let-down."
About 50 years later, the biochemist Vincent du Vigneaud took up the potent pituitary substance. Throughout his career, du Vigneaud studied how structure relates to function in biologically important compounds, and he set out to define oxytocin's structure. By 1953, he had identified the nine amino acids, set them in the right order and handedness, and discovered the biologically important disulfide bond between two cysteines that creates a ring in the peptide hormone. To be sure he had it right, du Vigneaud synthesized the compound--the first synthesis of any peptide hormone. His work resulted in a Nobel Prize in Chemistry for du Vigneaud in 1955.
Synthetic oxytocin, also called Pitocin or Syntocinon, is now regularly prescribed to induce as well as augment labor. The Journal of the American Medical Association estimated in 1998 that 16% of labors are induced in the U.S., and an additional 16% of labors that start spontaneously are augmented with inducing drugs. Oxytocin is also administered just after birth to prevent postpartum hemorrhage if the uterus does not continue to contract and stop bleeding. Less commonly, a nasal spray of oxytocin is sometimes given to mothers who have trouble with milk let-down in the first few days of nursing.
For many years, researchers saw oxytocin primarily as a pregnancy hormone because of its starring roles in childbirth and nursing. Scientists are now, however, revealing many subtle, lifetime effects of oxytocin in both men and women. Oxytocin, it turns out, functions much more broadly than scientists had realized.
Researchers began to suspect a broader role for oxytocin when they saw that the same receptor that reaches such high concentrations in the laboring uterus is found in other tissues in both men and women, including the brain, heart, and reproductive tract. Some researchers suspect, in addition, that there are one or more as-yet-unidentified oxytocin receptors.
Oxytocin plays a large, and largely unexplored, role in the brain. Oxytocin is not only a hormone that circulates in the bloodstream, it is also a neurotransmitter that travels along nerve cells in the brain and elsewhere. The cells that make oxytocin in the hypothalamus and send it to the pituitary gland also send oxytocin to different regions of the brain. Moreover, cells of the hypothalamus are not the only cells that make oxytocin. The ovaries, testicles, heart, and blood vessel walls have all been shown to produce their own oxytocin.
Blood and brain levels of oxytocin rise in instances outside of pregnancy and nursing. For example, during orgasm, oxytocin levels sharply peak in both men and women. (Oxytocin may facilitate the transport of sperm, some researchers suggest.) Animal studies also show that simply after pleasant warmth or rhythmic touch, oxytocin levels rise. Oxytocin injections in animals can, among other things, decrease blood pressure, encourage urination, and speed wound healing. Release of oxytocin in the brain reduces anxiety, increases the pain threshold, and reduces depression in animal models.
Oxytocin researcher Kerstin Uvns Moberg, professor of physiology at the Swedish University of Agricultural Sciences, suggests that oxytocin is the leading hormone in a physiological system that calms the body and promotes social bonding. Moberg writes in her book "The Oxytocin Factor" that oxytocin has the opposite effect of "fight-or-flight" hormones vasopressin and adrenaline, which increase stress, danger-readiness, and wariness of strangers. Oxytocin, she says, helps the body relax and encourages romantic, family, and pair bonding.
Her hypothesis is supported by studies that show social bonds are made when oxytocin levels are high. Female rats that receive an injection of oxytocin begin to display maternal behavior toward nearby rat pups whether the females have had offspring or not and whether the pups are theirs or not. If a female vole standing next to a male vole receives an injection of oxytocin, she will later show a preference for that male vole over others. In humans, oxytocin plasma levels were higher and blood pressure was lower in premenopausal women who said they got more hugs from a spouse or partner.
Such pleasant effects from one small peptide has stimulated research into creating an oxytocin pill. An intravenous drip for labor induction works fine--but for other indications, patients prefer something that can be swallowed. The stomach, however, breaks down peptides. Even once in the blood, oxytocin is inactivated within minutes by the enzyme oxytocinase. Getting an oxytocin drug into the brain is an even greater challenge. For the time being, we'll have to make do with more frequent hugs.
Did you know that Swiss researchers have recently reported that doses of oxytocin significantly increased the level of trust that people placed in strangers who were handling their money?