A radioimmunoassay for rabbit luteinizing hormone (rLH) in which rLH shows no significant cross-reaction with human LH (hLH) or human chorionic gonadotropin (HCG) was employed to test for the existence of a short-loop feedback for LH in the rabbit. Two weeks after castration, hCG and hLH were administered intravenously to rabbits, and the effects on circulating rLH were measured. Purified hLH (10 ng or 100 IU) produced significant depression of blood rLH within 30-60 min of intravenous injection. Saline administered to the same animals produced no changes in rLH. Injection of hCG (2,000 IU) under the same conditions also produced a significant fall in rLH. However, hCG administered to rabbits castrated 6 wk prior to study failed to suppress endogenous rLH. These data demonstrate, by direct radioimmunoassay quantification of blood hormones, the existence of a short-loop negative feedback for LH in the rabbit. They also suggest that the sensitivity of the short-loop changes with time after castration.

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Free alpha subunit chains of the glycopeptide pituitary hormones have been found in the sera of normal subjects and postmenopausal women. To ascertain whether the alpha subunit of LH is directly secreted by the pituitary or formed as a result of degradation of intact LY in the periphery, alpha subunits and intact LH were measured by radioimmunoassay in human volunteers after LRF stimulation and purified LH infusion. In 4 subjects a loading dose of 90 IU, followed by the infusion of 22.5 IJ of purified human LH over 30 min, produced peak serum LH levels of 41 mIU/ml but no change in alpha subunit levels of 35 IU of purified human LH to an additional 4 subjects, produced peak LH levels of 8* mIU/ml, but again, no change in alpha subunits. In the same two groups of subjects 100 mug of LRF produced peak LH levels of 25 mIU/ml and 75 mIU/ml, respectively, with significant alpha subunit elevations at 20 min of 1.7 ng/ml and 2.7 ng/ml, respectively. In separate groups of men LRF was administered over a wide dose range of 1 to 3,000 mug and LH and the alpha subunit measured. A dose-response curve existed over the entire LRF dose range for blood LH; no minimum or maximum plateaus were observed over the range studied. However, the alpha chain response appeared to reach a maximal plateau at a dose of 100 mug of LRF. The results are compativle with the hypothesis that the alpha subunits appearing in the peripheral circulation in response to LRF are due to secretion by the anterior pituitary and not due to peripheral degradation of intact secreted LH.

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