Prolactin metabolic clearance and resistance to dopaminergic suppression in acute uremia

A nephrectomized rat model was developed to examine PRL resistance to dopaminergic suppression, which is frequently present in humans with renal insufficiency. The MCR and the response of PRL to a dopamine (DA) infusion (0.4 microgram/kg . min) were measured in 24-h totally nephrectomized (TN) and sham-nephrectomized (SN) rats concurrently treated with alpha-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis. TN rats became significantly hyperprolactinemic within 1 day [36.2 +/- 7.1 vs. 18.5 +/- 2.5 (+/- SE) ng/ml; P less than 0.05]. SN and TN rats responded to AMPT with significant and sustained 3- and 5.5-fold increases in PRL, which DA reduced by 85% and 24%, respectively. Total nephrectomy decreased the PRL MCR by 58% (TN, 0.51 +/- 0.03; SN, 1.22 +/- 0.13 ml/min; P less than 0.001) and significantly increased the PRL secretion rate (TN, 79 +/- 10; SN, 37 +/- 8 ng/min; P less than 0.01). In the absence of DA infusion, AMPT reduced plasma DA to undetectable levels, while the median eminence DA contents in TN and SN rats were reduced to similar levels. Our data suggest that the totally nephrectomized rat is a suitable model to study PRL resistance to dopaminergic suppression, and that because DA does not cross the blood-brain barrier, the defect in uremia probably occurs at the level of the lactotroph.