C. Ohlsson et al., The relative importance of endocrine versus autocrine/paracrine insulin-like growth factor-I in the regulation of body growth, PED NEPHROL, 14(7), 2000, pp. 541-543
Body growth is regulated by growth hormone (GH) and insulin-like growth fac
tor-I (IGF-I). The classical somatomedin hypothesis of this regulation is t
hat 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 ab
olished IGF-I production in the livers of mice by using the Cre/loxP recomb
ination system. These mice displayed a more than 75% reduction in serum IGF
-I associated with increased serum levels of GH. In contrast, they demonstr
ated a normal postnatal growth, indicating that extrahepatic, autocrine/par
acrine-acting IGF-I is the main determinant of postnatal growth. Thus, the
"classical" somatomedin hypothesis needs revision. We propose the "dual som
atomedin hypothesis" according to which: (1) autocrine/paracrine IGF-I is t
he main determinant of postnatal body growth and (2) liver-derived, endocri
ne-acting, IGF-I exerts negative feedback on GH secretion and possibly also
exerts other effects on carbohydrate and lipid metabolism.