The mechanism may involve receptor proteins. The hypothalamus is connected to and regulates the pituitary gland. The hypothalamus - pituitary gland axis is the main link between the nervous system and the endocrine system and its hormones; cell receptors in the nervous system monitor the blood and the hypothalamus passes the information to the pituitary gland which, by its secretion of hormones, regulates the activity of other endocrine glands. For example, in the case of glucocorticoids, the pituitary gland regulates secretion from the adrenal cortex. The principal role of the system is to maintain homeostasis, or constant conditions. Programming permanently modifies the feedback systems that control growth. It is thought that it may involve changes in the sensitivity of the receptor proteins to hormone levels. If the sensitivity is permanently set to a different level this could lead to a corresponding change in the basal level of the circulating hormones.
The underlying cause is thought to be the interaction of the nutrient environment with the genome. Although the mechanism is not yet understood, gene expression would be permanently altered so that changes persist. Evidence for an interaction between genes and the environment comes from studies on the effect of polymorphisms within the Vitamin D receptor gene (VDR). It has been demonstrated that the effect of different VDR polymorphisms on an individual's BMD depends on their birth weight.