Dysregulation in the growth hormone/insulin-like growth factor-1 (GH-IGF-1) axis may play an important role in the developmental programming of metabolic disorders in adult offspring following maternal undernutrition (UN). We investigated whether pre-weaning GH treatment can reverse or ameliorate the programming effects in offspring following maternal undernutrition.
Female Sprague Dawley rats were fed either a chow diet ad-libitum (C) or 50% of ad-libitum (UN) throughout pregnancy. Litters were adjusted to 8 pups and all mothers fed chow ad-libitum after birth. From postnatal day 3, C and UN pups received either saline (CS and UNS) or GH (2.5ug/g/day, CGH and UNGH) daily throughout lactation. After weaning, 4 offspring (2 male and 2 female) were randomly selected from each litter and fed the chow diet for the remainder of the study (150 days). Body weights were recorded regularly. Plasma and liver tissue were collected from adult offspring for cytokine and gene expression analysis.
Pre-weaning GH treatment significantly reduced catch-up growth observed in male and female UN animals. Hepatic growth hormone receptor (GHR) expression was significantly increased in UNS offspring and normalised in male and female UNGH offspring. Hepatic IGFBP2 gene expression was significantly decreased in male and female UNS offspring and normalised by GH treatment in both sexes. Plasma IGF-1:IGFBP3 ratio was significantly increased in male and female UNS offspring compared to controls and was reduced in UNGH offspring. Plasma leptin levels were significantly elevated in female UNS offspring, reflective of an increased fat mass, and were normalised in UNGH offspring.
Our findings suggest that GH treatment during a critical developmental window might prevent maternal UN-induced catch-up growth and later adiposity and provides evidence that manipulation of the GH-IGF1 axis in early development may be a promising strategy to prevent adverse developmental programming effects in later life.