INFLUENCE OF LACTOTROPH CELL-DENSITY ON PROLACTIN SECRETION IN RATS

The relationships between the stimulation of prolactin secretion and proliferation of lactotrophs was studied from a multidisciplinary standpoint in three experimental models. Administration of both oestrogen and sulpiride resulted in a significant increase in prolactin secretion and in the lactotroph population. A single injection of 10-mu-g oestradiol benzoate (OB) induced a twofold increase in the proliferation of lactotrophs (morphometrically as volume density), which increased further (2.5-fold) after three OB injections. Parallel changes were observed in the net counts made on lactotrophs sectioned through the nucleus to avoid possible distortions in volume density caused by hypertrophic cytoplasms. Comparable results were obtained with the mitotic index in the same groups of rats exposed to treatment with colchicine. The effect of sulpiride on proliferation of lactotrophs was also significant (1.7-fold) but less pronounced than in rats treated with oestrogens. The treatments with oestrogen and sulpiride did not stimulate lactotrophic activity in a similar way, as judged by the levels of serum prolactin and the storage patterns of small and big prolactin in pituitary glands. Serum prolactin (mean +/- S.E.M.) in control ovariectomized rats was 4.0+/-0.9-mu-g/l and one and three injections of OB raised these levels to 14.4+/-5.0 and 28.8+/-4.6-mu-g/l respectively. The highest levels of serum prolactin were seen in sulpiride-treated rats (467.2+/-28.7-mu-g/l). Striking differences occurred in the pituitary contents of big prolactin, the control values increasing from 5.3+/-0.5 to 10.2+/-1.3-mu-g/mg after one OB injection and to 14.7+/-0.7-mu-g/mg after three OB injections. In contrast, the concentration of big prolactin in sulpiride-treated rats was very low (1.85+/-0.2-mu-/mg), 2.8-times smaller than the controls. Other changes were also found in the small prolactin content in pituitary tissue with higher values in all the experimental models. These differences could only be detected after differential extraction of big and small molecular forms of prolactin. In ovariectomized rats, treatment with several doses of oestrogen enhanced the proliferation observed in the lactotroph population and increased the number of mitoses. In turn, morphological data could be closely related to the higher levels of prolactin in serum and pituitary glands. A sustained stimulation of lactotrophic secretion was always followed by proliferation of lactotrophs, the number of which fluctuated in parallel with the degree of stimulation.