IGF-1 stimulates synthesis of undersulfated proteoglycans and of hyaluronic acid by peritubular cells from immature rat testis.
The exposure of confluent peritubular (PT) cells from immature rat testis to insulin-like growth factor-1 (IGF-1) induced a time and dose-dependent increase of [35S]-sulfate and [3H]-D-glucosamine incorporations in newly synthesized proteoglycans (PG). This increased content of PG was the result of an enhancement of PG synthesis rather than a decreased rate of degradation. IGF-1 had no effect on the molecular weight of synthesized PG nor on the nature and distribution of the constitutive glycosaminoglycan chains, both in medium and in cell layer. The stimulation of PG synthesis by IGF-1 appeared to be due, at least partially, to an increase of glycosylation processes. IGF-1 effect was mediated by the classical tyrosine kinase signalling process, since IGF-1 action on PG synthesis was abolished by genistein and tyrphostin A9, two well known tyrosine kinase inhibitors. The increase of PG synthesis was accompanied with an undersulfation of constitutive glycosaminoglycan (GAG) chains (chondroitin sulfate and heparan sulfate chains) since the [35S]/[3H] ratio was reduced by about 20-25% in presence of IGF-1. Although the mechanism of hyaluronic acid synthesis was completely different from those of other GAG, IGF-1 also dramatically enhanced its production by PT cells.
Thiébot
B
B
Laboratoire de Biochimie, EP CNRS 009, IRBA, Université de Caen, France.
Bichoualne
L
L
Langris
M
M
Bonnamy
P J
PJ
Barbey
P
P
Carreau
S
S
Bocquet
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016521:Electrophoresis, Gel, Pulsed-Field; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D005944:Glucosamine / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011509:Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013431:Sulfates / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D006027:Glycosides; D011509:Proteoglycans; D013431:Sulfates; C008646:4-nitrophenyl beta-D-xyloside; D007334:Insulin-Like Growth Factor I; D006820:Hyaluronic Acid; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005944:Glucosamine