[Growth hormone receptor and binding protein: roles in cellular responsiveness to growth hormone].
In most species, the structure of the growth hormone-binding protein (GH-BP) is identical to that of the growth hormone receptor (GH-R). The affinity (Ka) of the GH-BP is however 10 x lower than that of the receptor. Two mechanisms of production of the GH-BP have been described: in the human and the rabbit, the GH-BP is cleaved near the cellular membrane by proteolysis and shed into the extracellular compartment while in murine species, the serum GH-BP is produced by alternative splicing of the gene coding for the GH receptor. The GH-BP prolongs the 1/2 life of plasma GH, dampening the free GH levels during peaks and maintaining free hormone levels during troughs via the slow dissociation of GH from the complex GH-GHBP. By controlling free GH levels within and between peaks, GH-BP would thus play an important role in modulating GH action at the cellular level. In several physiological and physiopathological conditions, GH-BP and GH-R are coordinately regulated. However, there are situations such as during pregnancy or certain periods of development where these 2 proteins are not co-expressed. Therefore, GH-BP circulating levels do not necessarily represent cellular GH-R concentrations. In the rat, GH-BP and GH-R are regulated by nutritional and endocrine factors, among those are GH, insulin and gonadal steroids. In the human, the mechanism responsible for the increase of the circulating GH-BP during infancy is still unknown. Finally, the eventual role of GH-BP in transmitting the intracellular message of GH following its binding to the receptor is still unknown.
Maes
M
M
Département de Pédiatrie, Cliniques Universitaires Saint-Luc, Faculté de Médecine, Université Catholique de Louvain, Bruxelles, Belgique.
Maiter
D
D
Massa
G
G
Ketelslegers
J M
JM
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D011247:Pregnancy; D051381:Rats; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D011986:Receptors, Somatotropin; D013006:Growth Hormone
Récepteur et protéine de liaison de l'hormone de croissance: rôles dans la réceptivité cellulaire à l'hormone de croissance.