Bovine lactoferrin as a Modulator of Neuroendocrine Components of Stress

Stress is a condition that maintains the homeostasis of the organism through the activation of different neuroendocrine pathways and secretion of a wide array of chemical mediators, including corticotropin-releasing hormone (CRH), neurotransmitters and glucocorticoids hormones. These molecules fulfill important physiological functions, but under stressful conditions, they can induce or aggravate a pathological state depending on type, severity and duration of stress. For this reason, the search for compounds that modulate the activity of the neuroendocrine pathways is crucial for the control of diseases associated with stressful situations. Bovine lactoferrin (bLf) is an iron-binding multifunctional glycoprotein that exhibits modulatory properties on the neuroendocrine system. Bovine lactoferrin affects the production and secretion of neuroendocrine components of the hypothalamus-pituitary-adrenal (HPA) axis. Neuroendocrine mechanisms of bLf entail either the down- or up-modulation of adrenal corticosteroids via HPA pathway activation, nitric oxide (NO) generation and opioid nervous system pathway activation. This manuscript is focused on reviewing the current contributions of bLf modulatory actions on the response of hormones, neurotransmitters involved in stress and behavior. Sustained use of drugs for stress-associated dysfunctions loses efficacy and requires the dose increase by tolerance and drug dependence. Therefore, bLf may be included as a therapeutic and/or adjunctive agent of drugbased therapies for the treatment of stress-associated emotional-disturbances.