Three peptides: LHRH, [DAla6, des-Gly NH2 10]LHRH/FSHRH-ethylamide (DAla6) and [D-Leu8, des-Gly NH210]LHRH/FSHRH-ethylamide (D-Leu6) were iodinated by a lactoperoxidase technique and separated from the mixture on QAE-A-25 Sephadex columns. In experiment I, 20 ovariectomized rats were used to evaluate competitive uptake of the monoiodinated D-Leu6vs. unlabeled D-Leu6 in various tissues. Rats were injected iv with either 0, 75, 225, 675 or 2025 ng of D-Leu6 followed 15 sec later by 17.5 ng labeled D-Leu6. The rats were exsanguinated 30 min posttreatment and serum and tissues were collected. A ratio of tissue cpm/mg to serum cpm/μl (T/S) was used to express uptake by each tissue. A decrease in uptake was found in the anterior pituitary tissue but not other tissues of rats injected with increasing doses of unlabeled analog. These data suggest that competition of labeled and unlabeled hormone was occurring for specific sites in the pituitary. In Experiment II the monoiodinated preparations were used to evaluate the time each hormone remained in the anterior pituitary and other tissues. Ovariectomized rats received an intracarotid injection of one of the three labeled peptides of Na 125I. Four rats from each group were exsanguinated at 5, 15, 30, 60, 120, 240 and 360 min after injection, and tissue and serum were collected. The D-Ala6 and D-Leu6 analogs were taken up to a greater degree in the pituitary and remained longer than the natural hormone. The increases in serum LH and FSH concentrations showed similar patterns with pituitary uptake of each peptide. The disappearance rates of all three peptides were similar. These data support the concept that increased pituitary uptake of the two analogs studied is the reason for their increased biological potency over natural LHRH/FSHRH.
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Reeves et al. (1977) studied this question.