Chronic Administration of Pharmacological Doses of Ovine Prolactin Decreases Hormone Disappearance Rate*

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Abstract
The disappearance of ovine PRL (oPRL) was measured by radioreceptor assay in blood serially drawn from the femoral vein of female Wistar-Furth rats after iv administration of 2 mg (35 U/mg; test dose). Serum oPRL was low before administration of the test dose. oPRL disappeared rapidly (t½ = 6-12 min) from the blood of rats not pretreated with oPRL and returned to normal levels 60–90 min after injection of the test dose. Disappearance curves showed only a single fast component. In contrast, rats pretreated with either 0.5 or 4 mg oPRL/day for 9–21 days had disappearance curves that could be resolved into two components: an initial fast rate (t½ = 5–18 min) and a slow rate (t½ = 40–259 min). Pretreated rats showed an increase in total hormone distribution volume and a decrease in the MCR, although no change in the initial distribution volume was detected. The longer the duration of pretreatment with oPRL (3–-25 days), the higher the serum oPRL concentration 4–5 h after injection of a test dose. Neither pretreatment with oPRL (4 mg/day) for 1 day nor treatment with bovine GH (4 mg/day), bovine serum albumin (4 mg/day), or estradiol (5 μg/day) for 10 days decreased the disappearance rate. No antibody was detected in the serum of pretreated rats by either gel chromatography or the Ouchterlony technique. Hence, the presence of antibody cannot explain the slower disappearance rate in pretreated rats. These findings permit us to achieve serum oPRL concentrations greater than 2000 ng/ml for 16–18 h with only two sc injections of 2 mg oPRL. The delayed disappearance of PRL from blood due to prior hormone exposure may be a phenomenon more general than appreciated. (Endocrinology106: 952, 1980)