Prolactin receptors in human pituitary adenomas

Abstract

In the rat, prolactin receptors (PRL-R) have been identified in normal pituitary cells and in anterior pituitary tumours induced by oestradiol. No published data are available concerning PRL-R in the human pituitary. The aim of our study was therefore to detect the presence of PRL-R in the normal human pituitary gland and human pituitary adenomas. Evaluation of free and total PRL-R in the normal pituitary gland and different pituitary tumours characterized by immunocytochemical analysis. Twenty-six unselected patients (14 M, 12 F) who underwent surgery for pituitary adenoma (3 prolactinomas, 4 GH-PRL adenomas, 5 GH adenomas, 1 ACTH adenoma, 9 glycoprotein and/or alpha-subunit adenomas, 4 null cells adenomas) were studied. Nine pituitaries from subjects whose death was unrelated to brain and endocrine diseases, were also studied as a control group in the PRL binding studies. Free PRL-R in microsomal membranes were determined by in-vitro radioreceptor assay using 125I-labelled human PRL as ligand. Total PRL-R were also measured in the same membrane fractions by removing endogenous PRL bound to its receptors using 4 M MgCl2. Serum PRL levels were also evaluated in all patients before surgery using an IRMA method. Specific binding values for PRL (free PRL-R) were 0.39 +/- 0.03% (range 0-1.96%) in the pituitary adenomas. These binding values were identical to those observed in normal pituitaries (0.38 +/- 0.07%, range 0.1-0.78%). Elevated PRL binding (1.25% and 1.96%) was found in two patients with PRL secreting adenomas and very high serum PRL levels (5768 and 11240 mU/I. No PRL binding was shown in 4 patients. Treatment of membranes with 4 M MgCl2 increased the specific binding (total PRL-R) in both pituitary tumours (0.5 +/- 0.11%; P < 0.001) and normal pituitaries (0.47 +/- 0.07%; P < 0.02). Our data have demonstrated the presence of prolactin receptors in normal cadaveric pituitary and in most pituitary adenomas, irrespective of histological classification. In particular, elevated prolactin receptor levels were shown in PRL-secreting tumours from patients with markedly increased serum PRL levels. Our study may support several lines of experimental evidence for a specific functional role for PRL in the growth of some pituitary adenomas.