Prolonged infusion of rat luteinizing hormone alters its metabolic clearance pattern: indirect evidence for postsecretory mutation of luteinizing hormone.

Constant rate infusion/stop-entry experiments of varied duration were done with rat pituitary LH to test the possibility that the relatively slow disappearance of endogenous circulating LH after hypophysectomy/stop-entry in orchidectomized rats might be due to redistributive distortion consequent to a prolonged "packing" of the extravascular LH spaces in these animals. The findings indicated that prolongation of LH infusion did result in progressive flattening of the decay curve after stop-entry. After 1 h of infusion, constant rate infusion/stop-entry decay of LH was nearly as rapid as decay after simple pulse injection of the same extract. After 24 h of infusion, it was nearly as slow as after hypophysectomy/stop-entry. However, this change could not be explained solely on the basis of redistribution, because a similar difference was seen when disappearance of "infused" and "injected" pituitary LH were examined by pulse injection of sera collected from rats which had been given this LH by injection or prolonged infusion. Although variations in extravascular LH "packing" might have influenced LH disappearance in the donor rats, there was no opportunity for such variations to develop in the recipients. Although the mechanism(s) involved in this progressive change in the metabolic clearance characteristics of exogenous (extracted) circulating LH might simply be selective accumulation of the molecules most capable for surviving in the blood, other possibilities exist (e.g. actual mutation of circulating LH molecules). Whether endogenous (secreted) LH undergone similar changes during its sojourn in the circulation is not yet known but these findings suggest that postsecretory mechanisms could contribute to the apparent qualitative difference(s) between stored and circulating rat LH. Several implications of this new information have been discussed.