Oxytocin, a mammalian hormone, is extremely interesting and has a variety of functions. Oxytocin was one of the first completely chemically characterized peptide hormones [2]. It is believed that oxytocin evolved from an ancient precursor hormone approximately 600 million years ago, around the time of vertebrate and invertebrate divergance. [1]
Oxytocin is a nonapeptide hormone, meaning it has an amino acid chain length of 9 residues. [2] As seen in the above image (Figure 1), a disulfide bond exists between the peptide's cysteine molecules at positions 1 and 6. This disulfide bond gives oxytocin a circular shape with a tri-peptide tail. [2]
The gene responsible for oxtocin's amino acid sequence is much larger then the actual hormone. It contains:
- an amino terminal signal peptide
- the oxytocin amino acid sequence
- neurophysin I amino acid sequence
- co-peptin - a carboxyl terminal peptide
The final products of this large gene after synthesis and cleavage include only oxytocin and neurophysin I.
Synthesis:
Oxytocin is a neurohypophyseal hormone meaning stored in the pars nervosa of the neurohypophysis. We most often refer to this tissue site as the posterior pituitary. [3]
It was originally believed that oxytocin was synthesized in the neurohypophysis, however, in the 1930's it was revealed that they are actually synthesized in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus, with a higher concentration of ocytocin synthesizing cells in the PVN. [2] These regions are clusters of cell bodies. [3]
Figure 2: Anatomy of the pituitary gland, the PVN and SON can be seen extending into the hypothalamus.
Active oxytocin is accompanied by an inactive binding protein called neurophysin I, or oxyphysin.
Synthesis occurs in the following steps:
- Translation into a into a large precursor protein, called pre-pro-oxytocin-neurophysin I (prepro-OT-NPI)
- Prepro-OT-NPI is stored in granules, called Herring bodies, and are carried along by axonal transport to the neurohypophysis (NOTE: the granules contain not only Prepro-OT-NPI, but also the enzymes that cleave the peptide chain to create the active hormone)
- Transport to the nuerohypophysis takes two hours and during this time the enzymes cleave the precursor to yield oxytocin and neurophysin which are then stored in the axonal endings of the pars nervosa
- Afferent impulses travel along the spinal cord to the brain stem, where they reach the PVN and SON and cause a depolarization whereby the action potential propogates along the hypothalamico-neurohypophyseal tract to the nerve terminals in the posterior pituitary
- A Ca2+ influx into the nerve terminal causes the exocytosis of the secretory granules, releasing oxytocin into the blood stream
Oxytocin release is regulated through independent nervous control. Nipple suckling, the activation of uterine stretch receptors, and even certain emotinal states have an effect on the secretion of oxytocin. These nervous responses will be discussed in the following section.
Function:
Oxytocin has many diverse functions which include:
- Stimulation of the uterus to begin contraction during childbirth
- The post pregnancy secretion of breast milk
- Affiliation with love: contributing to maternal behavior and positive social responses
Parturition
Oxytocin is known to play a very important role during pregnancy, particularly during birth. During pregnancy ooestrogens cause the secretion of oxytocin to be steadily increased, and also increase the concentration of oxytocin receptors in myometrium smooth muscle cells. [2] However, the actions of oxytocin are not in full effect until the end of the pregnancy because throughout pregnancy there is a high concentration of progesterone which overrides oxytocin receptor synthesis until its concentration decreases at the end of the pregnancy [3].
When the fetus is fully developed it causes the uterus to stretch, which signal uterine stretch recptors to act on the hypothalamus ordering it to release oxytocin [3]. Oxytocin then travels to to the uterine muscles where it binds to receptors and increases the intensity of uterine contractions. The result is a positive feedback loop, whereby increased contractions stimulate the uterine stretch receptors even more, resulting in further oxytocin secretion. [5] Oxytocin also causes the myometrial smooth muscle cells to secrete prostoglandins, which also funtion to aid the myometrium in contraction [3].
Once contractions cause the fetus to reach the cervix, the pressure stimulates mechanoreceptors which also have nervous connections to the hypothalamus, again increasing the release of oxytocin. This positive feedback causes the cervix to dialate, allowing the fetus to move through the cervic and vagina, thus resulting in birth. [3]
Lactation
Lactation occurs after parturition, and is the process of secreting milk for young through the breast. This is a very important trait to possess because milk is extremely important to the nutrition of mammalian newborns [3]. Oxytocin plays an extremely important role in lactation. When a newborn suckles for milk, the richly innervated nipple undergoes mechanical stimulation and sends the stimuli to the central nervous system which stimulates the release of oxytocin from the neurohypophysis. Oxytocin then travels to the myoepithelial cells surrounding the breast alveoli (where milk is stored) causing them to contract. [4] This contraction squeezes the alveolus forcing milk into milk ducks and finally exiting through the nipple. [3]
While continuous suckling creates a positive feedback on oxytocin release, the body can also develop a type of condition reflex that initiates oxytocin release. So when a mother hears a baby's cry, the nervous system will immediatly stimulate the release of oxytocin. Another interesing fact is that stiumlation of a males nipples also heighten plasma oxytocin levels, however the reasons behind this action are unknown. [3]
Social Functions
Oxytocin has actually been described as the neurohormone of affiliation resulting in maternal behavior and positive social responses. [6] Various studies have shown that when injected with oxytocin, many animals behave more friendly, and have reduced agression. Oxytocin expression is predominant in females as its primary functions are to allow for sucessful female reproduction, yet experiments show that males too have positive social responses when administered oxytocin. [6]
Oxytocin has also been linked to memory associated with positive social responses. For instance, when a positive social memory is created, and stimuli cause an individual to recall that memory, there is an accompanied increase in plasma oxytocin levels. Oxytocin levels also increase during positive social interactions such as touching. [8]
Maternal behavior has been shown to increase upon the injection of oxytocin. For instance, rats injected with oxytocin would group foster pups together in a corner, lick them, build nests, and retrieve pups if they were removed from the group. These behaviors were shown to be absent in rats who were not induced with oxytocin. [7]
This concludes my discussion of the brilliant hormone oxytocin. While many questions still remain regarding the social effects of oxytocin, it is clear that its high importance to mammalian physiology is definite. I hope this dicussion helped you to gain a great understanding and appreciation for this amazing hormone!
[1]Dirks, R W., Van Kesteren, R E., Smit, A B., With, N D., Geraerts, W P., and Joosse, J. 1992. Evolution of the vasopressin/oxytocin superfamily: characterization of a cDNA encoding a vasopressin-related precursor, preproconopressin, from the mollusc Lymnaea stagnalis. Endocrinology Proc. Natl. Acad. Sci. USA: (89) 4593-4597.
[2] Hadley, Mac E. 1998. Prentice Hall Inc.: New Jersey, USA.
[3] Hill, Richard W., Wyse, Gordon A., and Anderson, Margaret. 2004. Animal Physiology. Sinauer Associates: Sunderland, MA, USA.
[4] Gard, Paul. 1998. Human Endocrinology. Taylor and Francis: London, UK.
[5] Jones, Richard., and Lopez, Kristen H. 2006. Human Reproductive Biology. Elsevier Inc.: Oxford, UK.
[6] Pfaff, Donald W. 1999. Drive: Neurobiological and Molecular Mechanisms of Sexual Motivation. MIT Press:USA.
[7] Dawood, M. Y. 1984. Oxytocin. Eden Press: Quebec, Canada.
[8]Uvnas-Moberg, Kerstin. 1998. Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology: 23(8): 819–835.
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