The endocrine regulation of growth during early life: a nutritional perspective

Abstract

AbstractRecent advances in molecular biology have begun to identify many of the molecular mechanisms involved in the control of cellular differentiation and subsequent growth. However, while this information may ultimately permit manipulation of animal growth it is important to remember that the most essential factor for growth remains adequate nutrition. The high correlation of growth rate with milk intake in neonates reminds us that growth is highly dependent on the rapid establishment of enteral nutrition after birth. The endocrine changes consequent on this, as well as the supply of nutrients to support metabolic homeostasis, play important rôles in determining survival.Birth is associated with dramatic changes in the secretion and plasma concentrations of many hormones (including insulin, glucagon, growth hormone (GH), triiodothyronine (T3), adrenaline and cortisol among others). However, while changes in secretion at this time may be of great significance for survival and adaptation during the perinatal period, after this it is only changes in the secretion of insulin and GH which appear closely related to neonatal growth. Sixty percent or more of variation in live-weight gain among lambs during the 1st month of life is positively associated with variation in plasma insulin levels, while associations with GH are strongly negative, despite the evidence for essentiality of GH as a promoter of insulin-like growth factor-1 (IGF-1) production. Observations on other species are consistent with those in lambs.Investigations in foetal lambs have established that insulin's crucial rôle as a primary regulator of anabolic metabolism and growth begins well before birth. However, while birth does not alter this important rôle, the establishment of enteral nutrition changes the way in which its secretion is modulated and increases its rôle as the principal endocrine regulator of glucose homeostasis. Secretion of gastrointestinal hormones in response to the first food plays an important rôle in this, modulating the secretion of insulin and promoting gut development through trophic actions on the mucosa. Insulin itself, also appears to have trophic effects on the liver and is probably an important determinant of nutritionally mediated alterations in hepatic IGF-1 production. Plasma IGF-1 concentrations, like those of insulin, are highly correlated with the rate of postnatal growth, but unlike insulin, the status of plasma IGF-1 as a direct regulator of cellular growth remains controversial. IGF-1 and the large molecular weight proteins to which it is bound in plasma are synthesized by many peripheral tissues as well as the liver and it seems likely that IGF-1, in association with other specific growth factors, acts principally in the extravascular compartment, as a local paracrine/autocrine regulator of cellular differentiation and growth. Whatever the status of the plasma IGF-1 pool its concentration appears to act as a useful index of the rate of tissue growth. While GH is essential for normal postnatal growth and the production of IGF-1, it does not appear rate-limiting in relation to nutritionally determined variations in growth rate. This contrasts strikingly with its rôle in growth manipulation.