Functional maturation of the neuroendocrine system in the perinatal period: studies of the somatotropic axis in the ovine fetus.

Studies of the maturation of hypothalamic control of adenohypophyseal hormone secretion are reviewed with particular reference to the somato-tropic axis in the ovine fetus. In the ovine fetus, circulating growth hormone concentrations are 20-fold higher than postnatal concentrations falling in the 72 h prior to delivery. These high fetal growth hormone concentrations are postulated to reflect an immaturity of hypothalamic control mechanisms. Synthetic human growth hormone releasing factor (10 micrograms/kg) markedly stimulates fetal circulating growth hormone release between 77 and 135 days of gestation. The response decreases with advancing maturation. Thus fetal growth hormone release is not under maximal stimulation. Fetal growth hormone, thyrotropin and gonadotropin release is pulsatile in nature and the growth hormone and thyrotropin pulses have exaggerated amplitudes compared to the postnatal pattern. It is suggested that in each case, this enhanced pulsatility is a consequence of immature feedback loops. Stereotaxic lesioning of the fetal median eminence at 110 days of gestation abolishes the pulsatility of fetal growth hormone release. However the basal secretion of growth release remains elevated in some fetuses compared to postnatal growth hormone concentrations. The basis for this high basal rate of secretion is speculative but it is postulated to reflect immaturity of inhibitory control mechanisms, in particular of the negative feedback loop. Neuropharmacological studies of circulating growth hormone release in the perinatal period are reviewed. These demonstrate that the potential for many neurotransmitters to influence fetal circulating growth hormone release has differentiated by midgestation. However antagonist studies have not demonstrated a tonic role for any stimulatory neurotransmitters, only for the inhibitory neurotransmitter, GABA. Growth hormone does not exert a major influence upon fetal growth. Studies of the ontogeny of growth hormone receptors in the ovine liver show that somatotropic receptors are first detected in the newborn lamb suggesting receptor immaturity as the basis for this lack of an effect of growth hormone in utero. The two insulin-like growth factors, IGF-I and IGF-II show different patterns of secretion in the perinatal period. IGF-I levels are low in utero, rise gradually through gestation with a marked postnatal rise perhaps related to the development of hepatic growth hormone receptors. IGF-II levels are high in the fetus and fall over the 3 days prior to delivery but are not affected by fetal decapitation. The role of placental lactogen as a stimulus of fetal IGF-II secretion is suggested.(ABSTRACT TRUNCATED AT 400 WORDS)