Developmental effects of ghrelin

Abstract

Ghrelin is a pleiotropic hormone that was originally described as promoting feeding and stimulating growth hormone release in adults. A growing body of evidence suggests that ghrelin may also exert developmental and organizational effects during perinatal life. The perinatal actions of ghrelin include the regulation of early developmental events such as blastocyst development and perinatal growth. Moreover, alterations in perinatal ghrelin levels result in structural differences in various peripheral organs, such as the pancreas and gastrointestinal tract. Recent data have also suggested that ghrelin acts on appetite-related brain centers in early life. Together, these observations indicate that exposure to factors that alter how ghrelin impacts development may induce lasting effects on physiological regulation.

Figure 1. Primary sites of expression and developmental effects of perinatal ghrelin

Ghrelin immunoreactivity (green fluorescence) is detected in both the pancreas and stomach of P10 mouse pups (A, B). Postnatal stomach ghrelin expression increases gradually to reach adult-like levels by 3–5 weeks of life (A). Meanwhile, pancreatic ghrelin expression declines progressively and is barely detectable in the adult pancreas (B). See Supplemental Online Material for detailed methods. Instead of regulating food intake, perinatal ghrelin appears to be an important signal for the growth and development of various tissues, including the pancreas, gastrointestinal tract, and central nervous system (C).

Figure 2. Ghrelin acts on appetite-related brain regions during neonatal life

In contrast to adults, acute ghrelin injection in P10 mouse pups does not result in changes in body weight (A). However, neurons located in the arcuate nucleus of the hypothalamus (ARH) contain GHSR immunoreactivity (red fluorescence) at P10 (B). Ghrelin increases the number of cFos-immunopositive cells (a marker of neuronal activation) in P10 ARH neurons 120 min after ghrelin injection (2 mg/kg, i.p.) (C). Acute ghrelin injection (2 mg/kg, i.p.) also increases Npy mRNA expression (D), while it decreases Pomc mRNA expression (E) in the hypothalamus of P10 mice. See Supplemental Online Material for detailed methods.