Hormones in Mother’s Milk Influence Baby’s Behavior

In March, Nicholas Day at SLATE wrote a column about the science of breastmilk, showcasing the emerging perspective that “Milk is food; Milk is Medicine; and Milk is Signal.” People seemed particularly intrigued by the hormonal ‘Milk is Signal’ aspect of mother’s milk, although it’s the least understood.

Sidebar: Why don't more kid costumes come in adult sizes. 

Seriously.

Recently, Skip Bartol and colleagues coined the term “lactocrine programming” to describe the process by which hormones present in mother’s milk permanently shape physiological processes within in the young (Bartol et al. 2009). A growing body of evidence has demonstrated that hormones from the mother, ingested through milk, bind to receptors within the young. Once these “maternal-origin” hormones bind, they seemingly trigger hormonal signaling cascades as would the young’s own hormones. Previously I described that hormones present in milk-specifically adiponectin- are associated with infant growth although the mechanisms within the infant remain unknown.

But mammalian young are not just passive creatures allocating mother’s milk solely to survival and growth. The calories young need to be behaviorally active, from the hesitant romping of the young foal to the arm-waving, ear-splitting tantrum of a newborn baby, come from mother’s milk. But other bio-active constituents in mother’s milk, namely hormones, may also influence HOW the infant behaves.

Some hormonal pathways underlie our behavioral tendencies- our individual predilection toward impulsivity, aggression, shyness, extroversion, etc. The phenomenon of individual behavioral tendencies is variably known as temperament, personality, or behavioral syndrome, depending in part on one’s professional field (Hinde 2013). The endocrine pathway of particular interest to behaviorists is the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is colloquially referred to as the “stress axis” because it is activated when individuals are in danger, social conflict, or perceive that they are under stress (such as having to finalize my poster in time to give it this afternoon at Experimental Biology 2013). The adrenal glands at the end of this pathway produce glucocorticoids (cortisol in primates and corticosterone in rodents) that serve important metabolic, immunological, and neurobiological functions.  For example, glucocorticoids regulate the use and storage of glucose and fats to meet energy needs during fight or flight.

There are too many epic things happening here.

What might this mean for infants? Well, glucocorticoids present in the mother’s blood circulation end up in milk, are absorbed intact across the infant’s intestinal tract (the epithelium), and bind to glucocorticoid receptors in the infant’s intestinal tract (Angelucci et al., 1983; Pácha 2000). For this reason, cortisol in mother’s milk likely reflects the mother’s environment and degree of danger or social conflict she encounters- it's an “honest” signal of her own HPA-axis activation. Most interestingly, the density of glucocorticoid receptors in the intestinal tract of mammalian young decrease after weaning. This tantalizingly suggests that those receptors are present specifically to receive cortisol signals from mother’s milk (Pácha 2000). Importantly we now know that glucocorticoids ingested via mother’s milk are shaping the HPA-axis and behavioral tendencies of offspring.

Tastes like STRESS!* YUM**

 photo by K. West

*Technically tastes like "up-regulation of the maternal HPA-axis" which does not necessarily mean the mother is stressed. For example, cortisol spikes in the wee hours of morning while you are still asleep to jump start being awake and facing your day.

**One study has shown that milk higher in fat and protein is also higher in cortisol, so it probably does taste YUM but not because of the cortisol (Sullivan et al. 2011).

A series of elegant experimental studies in rats by Angelucci, Catalani, and Casolini’s research group in the Department of Human Physiology and Pharmacology, University of Rome represents the most comprehensive investigation of ingested glucocorticoids on behavioral, cognitive, and physiological outcomes for any mammal. Their studies indicate that ingestion of glucocorticoids via mother’s milk have beneficial programming effects in offspring that persist into adulthood. In their study design, rat dams consume glucocorticoids in their water, increasing glucocorticoids in their blood and their milk. 

Full Disclosure: Red-eyed rats freak me out. 

As juveniles, individuals who ingested elevated glucocorticoids through their mother’s milk had better spatial memory (Catalani et al 1993, Casolini 1997). In adulthood, these individuals demonstrated better coping behavior during stress challenges- they showed less anxiety and more exploration (Catalani et al 2000, Catalani et al 2002, Meerlo et al. 2001). The elevated glucocorticoids in mother’s milk altered areas of the brain that regulate the physiological stress response (Catalani 2000). Interestingly these neurobiological effects were only seen in males, not females, even though the behavioral effects were similar in both sexes. These rodent studies demonstrate, using the gold standard of experimental manipulation, that hormones in mother’s milk shape behavioral outcomes in offspring, but that the neurobiological pathways may differ subtly for sons and daughters.

Although these effects have only been experimentally demonstrated in rodents, correlational data from monkeys and humans suggests something similar may be going on. In a sample of 44 rhesus monkey mothers, we found substantial individual variation in cortisol concentrations in milk. Infants whose mothers produced higher concentrations of cortisol in milk were characterized as more “Confident”, a factor score derived from systematic ratings of confident, bold, active, curious, and playful trait adjectives. However this effect was driven by sons- milk cortisol concentrations did not predict ‘Confidence’ factor scores in daughters (Sullivan et al. 2011). The results from monkeys are partially consistent with the results from rodents- glucocorticoids ingested through mother’s milk are associated with less fearful, more exploratory tendencies, but only for sons.

UPDATE November 2014: New findings expand and complicate the story of hormones in rhesus monkey milk. Details HERE.

“Where do you think you’re going, buddy?” 

photo by K. West.

In 2007 a study of 253 human infants provided suggestive evidence that cortisol in breast milk may also contribute to behavioral tendencies in humans (Glynn et al. 2007). Breast-feeding mothers with higher plasma cortisol concentrations, used as a proxy for milk cortisol concentrations, rated their infants as significantly more fearful than did breastfeeding mothers with lower plasma cortisol concentrations. Importantly, maternal cortisol concentrations were not associated with infant fearfulness among mothers who were formula-feeding their infants. These data suggested that the cortisol ingested via milk directly contributed to infant fearful temperament, rather than maternal cortisol influencing behavioral care of the infant or the mother’s rating of her infant’s temperament (Glynn et al. 2007).

Recently the same research team directly investigated cortisol concentrations in milk among 52 breast-feeding mothers (Grey et al. 2012). Grey and colleagues discovered that higher concentrations of cortisol in breastmilk were associated with greater “Negative Affectivity.” This is a composite score of the infant’s tendency toward fear, sadness, discomfort, anger/frustration, and reduced soothability as reported by the infant’s mother. These results were not explained by other factors such as maternal depression or perceived stress. And most interestingly, the effect was driven by daughters- the relationship between milk cortisol concentrations and negative affectivity was not present in sons!

photo by Jill Greenberg

These foundational studies demonstrate effectively that ingested glucocorticoids are predictive of infant behavior. Additionally sons and daughters may have different sensitivities to maternal hormones for reasons that remain unclear. Interestingly the human results differ markedly from findings in both monkeys and rats; in humans ingested glucocorticoids seemingly make infants more fearful and the effect is present in daughters but not sons. The reverse was found in monkeys- milk cortisol was associated with outcomes in sons but not daughters. In rodents the behavioral outcomes are present in both sons and daughters, but the neurobiological pathways underlying the outcomes differ between sons and daughters. Different milk for sons and daughters and/or different responses of sons and daughter to mother's milk are seriously cool. And cortisol is just ONE hormonal signal- there are possibly many more hormones and other bioactives that could affect infant behavior:

SO MUCH TO STUDY! SO LITTLE GRANT FUNDING!

If you are particularly interested- this paper provides A LOT more info & is written for an undergraduate audience.

Citations:

Angelucci L, Patacchioli FR, Chierichetti C, Laureti S. 1983. Perinatal mother-offspring pituitary-adrenal interrelationship in rats: corticosterone in milk may affect adult life. Endocrinol Exp. 17(3-4):191-205.

Bartol FF, Wiley AA, Bagnell CA.  Relaxin and maternal lactocrine programming of neonatal uterine development.  Annals of the New York Academy of Sciences  1160:158-163, 2009.

Casolini P, Cigliana G, Alemà GS, Ruggieri V, Angelucci L, Catalani A. 1997. Effect of increased maternal corticosterone during lactation on hippocampal corticosteroid receptors, stress response and learning in offspring in the early stages of life. Neuroscience. 79(4):1005-12.

Catalani A, Casolini P, Cigliana G, Scaccianoce S, Consoli C, Cinque C, Zuena AR, Angelucci L. 2002. Maternal corticosterone influences behavior, stress response and corticosteroid receptors in the female rat. Pharmacol Biochem Behav. 73(1):105-14.

Catalani A, Casolini P, Scaccianoce S, Patacchioli FR, Spinozzi P, Angelucci L. 2000. Maternal corticosterone during lactation permanently affects brain corticosteroid receptors, stress response and behaviour in rat progeny. Neuroscience. 100(2):319-25.

Catalani A, Marinelli M, Scaccianoce S, Nicolai R, Muscolo LA, Porcu A, Korányi L, Piazza PV, Angelucci L. 1993. Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance. Brain Res. 624:209-15.

Glynn LM, Davis EP, Schetter CD, Chicz-Demet A, Hobel CJ, Sandman CA. 2007. Postnatal maternal cortisol levels predict temperament in healthy breastfed infants. Early Hum Dev. 83(10):675-81.

Grey KR, Davis EP, Sandman CA, Glynn LM. 2012. Human milk cortisol is associated with infant temperament. Psychoneuroendocrinology. pii: S0306-4530(12)00358-7. Epub ahead of print doi: 10.1016/j.psyneuen.2012.11.002.

Hinde K, Capitanio JP. 2010. Lactational programming? Mother’s milk predicts infant temperament and behavior. Am J Primatol. 72:522-529

Hinde K. 2013. Lactational programming of infant behavioral phenotype In: Primate Developmental Trajectories in Proximate and Ultimate Perspectives. Clancy KBH, Hinde K, Rutherford JN, eds.  Springer, New York. pp 187-207

Meerlo P, Horvath KM, Luiten PG, Angelucci L, Catalani A, Koolhaas JM. 2001. Increased maternal corticosterone levels in rats: effects on brain 5-HT1A receptors and behavioral coping with stress in adult offspring. Behav Neurosci. 115(5):1111-7.

Pácha J. 2000. Development of intestinal transport function in mammals. Physiol Rev. 80(4):1633-67.

Sullivan EC, Hinde K, Mendoza SP, Capitanio JP. 2011. Cortisol concentrations in the milk of rhesus monkey mothers are associated with confident temperament in sons, but not daughters. Dev Psychobiol 53: 96–104.

Note: A previous version of this post was featured in the February Issue of SPLASH! Milk Science Update