Uptake of Iodinated Luteinizing Hormone Releasing Hormone Analogs in the Pituitary1

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Abstract
Three peptides LHRH/FSHRH [luteinizing hormone releasing hormone/follicle stimulating hormone releasing hormone], [D-Ala6, des-Gly NH210]LHRH/FSHRH-ethylamide [D-Ala6) and [D-Leu6, 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-Leu6 vs. unlabeled D-Leu6 in various tissues. Rats were injected i.v. with either 0, 75, 225, 675 or 2025 ng of D-Leu6 followed 15 s later by 17.5 ng labeled D-Leu6. The rats were exsanguinated 30 min post-treatment and serum and tissues were collected. A ratio of tissue cpm/mg to serum cpm/.mu.l (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. Competition of labeled and unlabeled hormone probably 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 1 of the 3 labeled peptides of Na 125I. Rats [4] 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 [Luteinizing hormone] and FSH [follicle stimulating hormone] concentrations showed similar patterns with pituitary uptake of each peptide. The disappearance rates of all 3 peptides were similar. These data support the concept that increased pituitary uptake of the 2 analogs studied is the reason for their increased biological potency over natural LHRH/FSHRH.