Oxytocin is most known for its functions in reproductive biology. The oxytocin receptor is encoded into a single-copy gene that is expressed through uterine smooth muscle cells, and myoepithelial cells of the mammary alveoli. [1]
Oxytocin functions to contract smooth muscle cells by binding to its heptahelical G-protein receptors. When bound to the receptor, inositol triphosphate, and diacylglycerol are formed. These compounds increase intracellular calcium and activate protein kinase C which plays a role in phosphorylating membrane calcium channels which thus further increasing the levels of intracellular calcium. The increased influx of calcium results in the binding of calcium to calmodulin in muscle cells, which activates myosin and thus results in the contraction of endometrial and myoepithelial cells. [1]
Interestingly, oxytocin is said to have increased release from the neurohypophysis during sexual intercourse. This release may cause uterine contractions which is hypothesized to help the transport of sperm reach the ova. This hypothesis stems from the idea that sperm cannot reach the ova at the rate they due using simply their flagella. [2] However, this theory is speculative because a non-pregnant uterus is insensitive to oxytocin. Another hypothesis to help explain the uterine contractions is the increased amount of catecholamines during intercourse which may stimulate uterine activity. [2]
Oxytocin's role in parturition is very significant. Oxytocin concentrations heighten considerably during the final stages of labor. This increase occurs because the dilation of the cervix, and full development of the fetus can stimulate stretch receptors in the uterus to act on the hypothalamus to stimulate oxytocin release. In response the increased levels of oxytocin, the sensitivity of the myometrium of the uterus to the hormone increases. This is illustrated through the increased concentration of oxytocin receptors via estrogen increase. [2] This is important because oxytocin causes uterine contractions during labour, acting in a positive feedback loop to increasing contractions which ultimately helps to facilitate the transport of the fetus through the uterus, exiting through the vagina. [2]
Lactation is stimulated by the suckling of an infant on the mother's nipple, resulting in the milk letdown, or milk ejection reflex. [1] The natural pulsatile release of oxytocin occurs after parturition when the areolae and nipples of the breast are mechanically stimulated through infanct suckling. These stimuli are conducted by afferent neural pathways to the neurohypophysis where oxytocin is synthesized and released in the paraventricular nuclei. [2] Interestingly, the neural pathways are ipsilateral, meaning they occur on the same side as the nipple being suckled. [2]
Figure 1: The milk ejection reflex stimulated by oxytocin release from the neurohypophysis.
Oxytocin plays an important role in social cognition and behaviour. Both males and females are shown to have positive social responses when administered oxytocin, even though oxytocin predominates in females during lactation and parturtion. [3] When interacting in positive social responses, and remembering positive social interactions, oxytocin levels increase. [4] Maternal behavior is often displayed and enhanced when oxytocin levels are increased. [5] While not well understood, it is obvious that an important link exists between positive social behaviors and oxytocin.
Pathology
Induced Labor:
Pregnant women whom it is deemed necessary to initiate early labor, or labor because the pregnancy has gone too long overdue, are induced. When a baby is overdue, it is still growing inside the womb. If the baby grows too large the endometrium may not be able to supply a sufficient amount of required nutrients to the baby. [5] Vaginal birth may also be difficult if the baby is very large, and a caesarean section (or removal of the fetus externally through an incision in the lower abdomen) may be necessary. Thus inducing the labor may reduce the need for a c-section. Induced labor first involves manually breaking the fluid sac, followed by the intravenous injection of oxytocin,which causes labor contractions [5] as previously described. However, there are some negative effects that oxytocin injections cause which include:
- hypertonicity
- uterine rupture
- and fetal bradycardia (or low heart rate)
The benifits of labor induction however far outweigh the risk factors. [5] Some of the complications oxytocin induced labor prevent are:
- maternal diabetes
- Rhesus isoimmunization (fetus and mother blood incompatibility)
- pre-eclampsia (Pregnancy induced hypertension because of increased serum proteins)
- premature rupture of the membranes
Thus if the pregnant individual shows signs of medical conditions that can be treated or prevented through the induction of labor, then induction should be administered. However, personal elected labor induction should be avoided as there are risk factors associated with oxytocin induced labor. [5]
NOTE: The following descriptions represent theories regarding oxytocin in relation to the pathological conditions cancer and autism. These theories are still being studied, and are described to provide a possible future outlook for oxytocin use in these conditions.
Cancer:
It was very interesting to discover that oxytocin may play a role in growth inhibition of tumors. Oxytocin receptors have recently been found in tissues other than the myo- and endometrium, and myoepithelial cells of the breast. For instance, it has been found in the vasculature, prostate, and bone tissues. [6] Oxytocin receptors have been found in breast carcinomas, and breast cancer cell lines, lung carcinomas, and a variety of other cancerous tissues. Growth inhibition is thought to occur through a non-conventional signalling pathway, cAMP-PKA, and has been shown in oxytocin treatments to neoplastic cells of the previously listed tissues. In these cases, oxytocin may actually help to stop the growth of tumors that have oxytocin receptors. [6] While the exact effects that oxytocin has on tumor growth in a variety of tissues needs to be further investigated, localized treatments of oxytocin may serve as a treatment for cell proliferation if future studies prove its effectiveness. [6]
Autism:
As previously mentioned, oxytocin plays a role in social behavior and memory. Thus it is interesting to explore the effects that oxytocin has on disorders that affect social cognition, such as autism. Autism effects speech and communication, causes impaired social functioning, and repetitive behaviors. [7]Autism patients do not have the same desire to form social bonds, which is thought to be facilitated through oxytocin, thus the connection between oxytocin and autism is obvious. Interestingly, theorists believe that oxytocin may serve as a future treatment to adult autism patients. Studies have shown that individuals with autism often fail to assign significance to speech. For example, one study tested autistic patients ability to recognize different tones such as happy, or angry in random phrases such as "The game ended at 4 o'clock." [7] Some patients were administered placebos whereas other patients were administered oxytocin. The study showed a positive result of processing and retaining social information when oxytocin was injected that was not as significant when placebos were administered. Repetitive behaviours of the individuals also were reduced upon oxytocin administration. [7]
This study suggests that oxytocin may indeed help social cognition in oxytocin individuals. While further studies are needed, the injection of oxytocin in young individuals seems promising, and may further help their cognitive development.
While the uses of oxytocin are still being discovered, this amazing hormone exhibits a promising potential to common and extreme pathologies such as cancer and autism. Because of the wide variety of social cognitive disorders, the possibilities for positive use of oxytocin may be endless. It will be exciting to see what the future holds for the use of oxytocin, and hopefully the decrease in severity of many pathological conditions!References:
[1] Jones, Richard., and Lopez, Kristen H. 2006. Human Reproductive Biology. Elsevier Inc.: Oxford, UK.
[2] Goodman, Maurice H. 2003. Basic Medical Endocrinology. Academic Press: San Diego, California.
[3]Pfaff, Donald W. 1999. Drive: Neurobiological and Molecular Mechanisms of Sexual Motivation. MIT Press: USA.
[4]Uvnas-Moberg, Kerstin. 1998. Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology: 23(8): 819–835.
[5] Dawood, M. Y. 1984. Oxytocin. Eden Press: Quebec, Canada.
[6]Kastin, Abba J. 2006. Handbook of Biologically Active Peptides. Academic Press.
[7] Hollander, E., Bartz, J., Chaplin, W., Phillips, A., Sumner, J., Soorya, L., Anagnostou, E., and Wasserman, S. 2007. Oxytocin Increases Retention of Social Cognition in Autism. Biol Psychiatry, 61: 498-503.
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