The relative importance of endocrine versus autocrine/paracrine insulin-like growth factor-I in the regulation of body growth.

• Body growth is regulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I). The classical somatomedin hypothesis of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have recently abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice displayed a more than 75% reduction in serum IGF-I associated with increased serum levels of GH. In contrast, they demonstrated a normal postnatal growth, indicating that extrahepatic, autocrine/paracrine-acting IGF-I is the main determinant of postnatal growth. Thus, the "classical" somatomedin hypothesis needs revision. We propose the "dual somatomedin hypothesis" according to which: (1) autocrine/paracrine IGF-I is the main determinant of postnatal body growth and (2) liver-derived, endocrine-acting, IGF-I exerts negative feedback on GH secretion and possibly also exerts other effects on carbohydrate and lipid metabolism.

Nyckelord

Animals

Autocrine Communication

physiology

Endocrine Glands

physiology

Growth

physiology

Growth Hormone

physiology

Humans

Insulin-Like Growth Factor I

physiology

Paracrine Communication

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)