Distribution and Disappearance of Radioimmunoassayable Circulating Luteinizing Hormone in the Rat: An Apparent Difference between Stored and Released Forms of the Hormone*

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Abstract
The distribution and disappearance of homologous LH [luteinizing hormone] in the rat were examined by several techniques, including a constant rate infusion/stop-entry (CRISE) method which had not previously been used for this purpose. The CRISE method offers 2 unique advantages over the pulse injection (PI) methods previously used for estimating the distribution volume (V) and decay constant (k) of a hormone. One advantage is that it allows V and k to be estimated when inner and outer LH pools are at equilibrium, rather than in the nonequilibrium situation immediately after the hormone is given by PI. The other advantage is that it allows intrinsic direct testing of these equilibrium estimates of V and k, not only at equilibrium but under the sort of preequilibrium conditions which commonly occur physiologically, i.e., during the early part of an LH surge. PI and CRISE studies of the LH present in rat pituitary extract yielded a similar metabolic clearance pattern (MCP) but different estimates of VLH. The initial segment of the MCP resembled an exponential curve (k .simeq. 2.1 h-1) for about 3 half-lives. After this the curve flattened (k decreased). Both equilibrium and nonequilibrium estimates of V and k were tested in the first order equation for constant rate infusion, [LH]t = IR(1--kt)/V .times. k, at several known infusion rates (IR). With the equilibrium estimates, the equation seemed to describe the effects of IR on plasma [LH] perfectly at all times, including the initial preequilibrium period. Findings for circulating exogenous pituitary LH were compared with findings for endogenous plasma LH, obtained by hypophysectomy/stop-entry (HxSE). Initial (equilibrium) estimates of k were similar by both methods. However, the initial segment of HxSE decay curves was relatively short; the MCP flattened (k decreased) after only 2 half-lives. The overall metabolic disappearance of plasma LH after HxSE seemed slower than that of injected or infused pituitary LH after PI or CRISE. Plasma LH and pituitary LH may be different and clearance parameters for the latter may not be valid for the former. A separate study deals with mechanisms through which this apparent species difference might develop.