Oxytocin is a posterior pituitary, or neurohypophysial, hormone.  Oxytocin was originally detected
as early as 1895, and its uterine-contracting and milk-ejecting properties were first described in the
early 1900’s.  The specific amino acid sequence and structure of oxytocin was first described and
chemically synthesized in the early 1950’s by du Vigneaud, for which he won the Nobel Prize in
Chemistry in 1955.  The subsequent development of specific agnonists and antagonists for oxytocin
has provided the platform for research to further elucidate the role of this peptide on physiology and
behavior (see Caldwell and Young, 2006, for further detail).

Since the 1950’s, research examining the role of oxytocin on the brain and behavior has flourished,
although a majority of this research has examined the role of oxytocin within non-human animal
models.  The direct mammalian female reproductive roles of oxytocin were among the first to be
identified.  Peripherally, oxyotcin is known to stimulate such female mammalian functions as milk
ejection during lactation and uterine contraction at parturition (Burbach et al., 2006).

A burgeoning literature indicates that oxytocin also plays a central role in the regulation of affiliative
behaviors, social attachment, and stress responses within animal models. For example, oxytocin
stimulates social motivation and approach behaviors, and facilitates formation of selective
mother-infant attachment and adult pair-bonds (see Lim & Young, 2006 for a recent review).
Oxytocin is also released both centrally and peripherally with stress (Nishioka et al., 1998;
Wotjak et al., 1998), and appears to have an anxiolytic effect on endocrine and behavioral systems
(Windle et al, 1997).

As compared with the animal literature, human research on the role of oxytocin is in its infancy.
Studies of lactating mothers indicate that suckling and nipple stimulation are associated with an
increase in oxytocin (Carter & Altemus, 1997).  Studies evaluating associations between peripheral
oxytocin levels and either affiliative or stress responses in non-lactating humans have, however, been
more mixed.

Measurement Issues

Conflicting results within the limited human oxytocin literature may, in part, represent
methodological issues associated with the peripheral measurement of this peptide.  First,
oxytocin is known to be released into peripheral circulation in a pulsatile fashion, where it has
a half-life of about 16 minutes (Amico, Ulbrecht & Robinson, 1987).  Thus, common use of
venipuncture for single blood draw assessments of this hormone may provide an incomplete
picture of regarding basal concentrations or variability of oxytocin over time or in response to
laboratory tasks.  Second, because oxytocin released centrally and peripherally are derived from
separate neuronal populations within the hypothalamus, peripheral oxytocin may or may not reflect
centrally released oxytocin.

The most common approaches to assessing peripheral oxytocin in humans includes the use of
in-house radioimmunassays (RIAs; for one example, see Amico et al., 1985) or commercially-
available assay kits, which include both RIA and enzyme immunoassay (EIA) approaches to
hormone measurement.  [For commonly used examples, see commercial kits available from
Assay Design (Ann Arbor, MI) or Peninsula Laboratories (Can Carlos, LA)].  The use of
commercially-available oxytocin assay kits are enjoying growing utilization in the human research
literature.   It is important to note, however, that commercially-available kits generally provide
significantly higher estimates of circulating oxytocin levels as compared with those obtained with
previously-described in-house RIAs.  It is not known what factors drive this measurement difference.
One possible explanation is that while previously studied in-house RIAs selectively target only the
biologically active, 9-amino-acid nonapeptide, alternate assays may assess both active oxytocin
as well as precursor molecules, or oxytocin prohormones.  While oxytocin prohormones are not
themselves believed to be biologically active, they may nonetheless represent plasma markers of
oxytocin production and activity and, research would suggest, are more sensitive to circulating
levels of estradiol.  To date, little research has directly compared results obtained from these
alternate oxytocin assays.

Relevant Human Research

Studies of lactating females support for the role of oxytocin in the modulation of cardiovascular
and HPA stress responses.  Suckling and nipple stimulation are associated with an increase in
oxytocin as well as a decline in cortisol concentrations in plasma (Carter & Altemus, 1997;
Chiodera et al., 1991).  Lactation in human females also appears to decrease stress reactivity,
dampening cortisol responses to physical (Altemus et al, 1995) and psychosocial (Heinrichs et al.,
2001) stressors.  Light et al. (2000) found that new mothers who showed endogenous increases in
plasma oxytocin levels after holding their baby displayed blunted blood pressure in response to a
subsequent psychosocial stressor.  Heinrichs et al (2003) found that male subjects who received
exogenous treatment with intranasal oxytocin in conjunction with social support exhibited lower
cortisol responses, decreased anxiety, and increased calmness during a subsequent stress task
(Heinrichs et al., 2003).  Similarly, a series of studies conducted by Light, Grewen and colleagues
indicate that endogenous peripheral oxyotcin release may be is associated with lower resting blood
pressure and lower sympathetic activity in pre- and postmenopausal women (Light et al 2005a,
2005b; Grewen et al., 2005).  In apparent contrast, however, Taylor et al. (2006) observed that
postmenopausal women reporting gaps or difficulties in their social relationships displayed
elevations in basal plasma oxytocin levels which were associated with elevated cortisol levels.
These results may point to the need to measure and conceptualize dynamic or interactive
aspects of peripheral oxytocin release and/or regulation, rather than rely solely on the
interpretation of static peripheral oxytocin levels.

References
Altemus M, Deuster PA, Gallivan E, Carter CS, Gold PW. Suppression of
hypothalamic-pituitary-adrenal axis responses to stress in lactating women.
J Clin Endocrinol Metab 80, 2954-2959, 1995.
Amico JA, Ervin MG, Leake RD, Fisher DA, Finn FM, Robinson AG.  A novel oxytocin-like
and vasotocin-like peptide in human plasma after administration of estrogen.  J Clin Endocrinol
Metab, 60:5-12, 1985.
Amico JA, Ulbrecht JS, Robinson AG.  Clearance studies of oxytocin in humans using
radioimmunoassay measurements of the hormone in plasma and urine.
J Clin Endocrinol Metab, 64:340-345, 1987.
Burbach JP, Young LJ, Russell J. Oxytocin: synthesis, secretion and reproductive functions.
In Neill JD (ed), Knobil and Neill’s Physiology of Reproduction. Elsevier, pp 3055-3128, 2006.
Caldwell HK, Young WS. Oxytocin and vasopressin: Genetics and behavioral implications.
In R. Lim (ed), Handbood of Neurochemistry and Molecular Neurobiology, 3rd ed, pp 573-607.
New York: Springer, 2006.
Carter CS, Altemus M. Integrative functions of lactational hormones in social behavior and
stress management. Ann NY Acad Sci 807, 164-174, 1997.
Chiodera P, Salvarani C, Bacchi-Modena A, Spallanzani R, Cigarini C, Alboni A, et al.
Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during
suckling or breast stimulation in women. Horm Res 35, 119-123, 1991.
Grewen KM, Girdler SS, Amico J, Light KC. Effects of partner support on resting oxytocin,
cortisol, norepinephrine, and blood pressure before and after warm partner contact.
Psychosomatic Medicine 67, 531-538, 2005.
Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact
to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54,
1389-1398, 2003.
Heinrichs M, Meinlschmidt G, Neumann I, Wagner S, Kirschbaum C, Ehlert U, Hellhammer
DH. Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial
stress in postpartum lactating women. J Clin Endocrinol  Metab 86, 4798-4804, 2001.
Kimura T, Saji F, Nishimori K, Ogita K, Nakamura H, et al. Molecular regulation of the
oxytocin receptor in peripheral organs. J Mol Endocrinol 30:109-115, 2003.
Light KC, Smith TE, Johns JM, Brownley KA, Hofheimer JA, Amico JA. Oxyotcin
responsivity in mothers of infants: A preliminary study of relationships with blood pressure
during laboratory stress and normal ambulatory activity.  Health Psychology 19, 560-567, 2000.
Light KC, Grewen KM, Amico JA. More frequent partner hugs and higher oxytocin levels are
linked to lower blood pressure and heart rate in premenopausal women. Biol Psychology 69,
5-21, 2005a.
Light KC, Grewen KM, Amico JA, Brownley KA, West SG, Hinderliter AL, Girdler, SS.
Oxytonergic activity is linked to lower blood pressure and vascular resistance during stress
in postmenopausal women on estrogen replacement. Hormones and Behavior 47, 540-548,
2005b.
Lim MM, Young LJ. Neuropeptidergic regulation of affiliative behavior and social bonding in
animals. Hormones and Behavior 50, 506-517, 2006.
Nishioka T, Anselmo-Franci JA, Li P, Callahan MF, Morris M.  Stress increases oxytocin
release within the hypothalamic paraventricular nucleus.  Brain Research, 781:57-61, 1998.
Sofroniew MV. Morphology of vasopressin and oxytocin neurons and their central and
vascular projections. Prog Brain Res 60, 101-114, 1983.
Swanson LW, Sawchenko PE.  Paraventricular nucleus: A site for the integration of
neuroendocrine and autonomic mechanisms.  Neuroendocrinol, 31;410-417, 1980.
Taylor SE, Gonzaga GC, Klein LC, Hu P, Greendale G, Seeman TE. Relation of oxytocin to
psychosocial stress responses and hypothalamic-pituitary-adrenocortical axis activity in
older women.  Psychosomatic Medicine 68, 238-245, 2006.
Windle RJ, Shanks N, Lightman SL, Ingram CD.  Central oxytocin administration reduces
stress-induced corticosterone release and anxiety behavior in rats.  Endocrinology,
138:2829-2834, 1997.
Wotjak CT, Ganster J, Kohl G., Holsboer F, Landgraf R, Engelmann M.  Dissociated central
and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress:
New insights into the secretory capacities of peptidergic neurons.  Neuroscience,
85:1209-1222, 1998.
 

Core-E MainBiological Measures Used