Ghrelin and the growth hormone secretagogue receptor in growth and development.
The pancreas is a major source of ghrelin in the perinatal period, whereas gastric production progressively increases after birth. Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth. However, ghrl(-/-) or ghsr(-/-) mice fed a high fat diet starting soon after weaning are resistant to diet-induced obesity, suggesting that ghrelin affects the maturation of the metabolic axes involved in energy balance. In addition, animal and human studies suggest that GHSR plays a physiological role in linear growth. In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake. In humans, a mutation of the GHSR gene that impairs the constitutive activity of the receptor was found in two families with short stature. Administration of acylated ghrelin to rat pups directly does not affect weight gain. In contrast, administration of ghrelin to pregnant or lactating rats results in greater fetal weight and postnatal weight gain, respectively, suggesting that maternal ghrelin may stimulate perinatal growth. These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.
Endocrinology and Diabetes Unit, Department of Pediatrics, British Columbia's Children's Hospital, University of British Columbia, 4480 Oak Street,Vancouver, British Columbia, Canada. jchanoine@cw.bc.ca
J-P
JP
Chanoine
K
K
De Waele
P
P
Walia
D000215:Acylation; D000293:Adolescent; D000328:Adult; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005215:Fasting / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism; D048788:Growth and Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007774:Lactation / Q000187:drug effects; D051379:Mice; D020125:Mutation, Missense; D010179:Pancreas / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000188:drug therapy / Q000378:metabolism; D011247:Pregnancy / Q000378:metabolism; D051381:Rats; D054440:Receptors, Ghrelin / Q000235:genetics / Q000502:physiology*
D054439:Ghrelin; D054440:Receptors, Ghrelin; D013006:Growth Hormone