Down-regulation in the insulin-like growth factor (IGP) axis during hibernation in the golden-mantled ground squirrel, Spermophilus lateralis: IG-F-Iand the IGF-binding proteins (IGFBPs)

The golden-mantled ground squirrel, Spermophilus lateralis, undergoes a pro found winter hibernation that represents, among other changes, a prolonged period of starvation. In addition to dramatic metabolic and other physiolog ical adaptations during hibernation which serve to reduce fuel energy expen diture, we have hypothesized that there may also be significant changes in the endocrine axis that regulates energetically-expensive somatic growth. A s compared with euthermic, non-hibernating controls, hibernating S. lateral is were found to have 75%-reduced serum concentrations of insulin-like grow th factor-I (IGF-I; from similar to 625 to similar to 150 ng/ml in both fem ales and males, P < 0.05). While IGFBP-3 was the predominant IGFBP in serum of the euthermic controls, its levels were reduced to a similar degree in serum from the hibernating animals. IGFBP-4 was present at relatively low l evels in the euthermic controls, and was reduced to undetectable levels in hibernating animals. Surprisingly, there was no IGFBP detectable in the 30 kDa range in either euthermic or hibernating S. lateralis, suggesting that IGFBP-1 does not play a role in hibernation-related changes in the IGF axis . In accordance with these endocrine changes, when serum from hibernating S . lateralis was added to cartilage explant cultures (at a 5% v/v concentrat ion), it exhibited no ability to alter S-35-proteoglycan synthetic rate, wh ereas serum from the euthermic squirrels significantly stimulated synthetic activity by 2-fold. These results suggest that part of hibernation adaptat ion in S. lateralis includes down-regulation in the growth-regulatory IGF a xis. J. Exp. Zool. 289:66-73, 2001. (C) 2001 Wiley-Liss, Inc.