REGULATORY ACTION OF PROLACTIN ON THE IN-VITRO GROWTH OF CD34+VE HUMAN HEMATOPOIETIC PROGENITOR CELLS

The pituitary hormone prolactin (Prl) is known to act as a local regul ator of immune cell function, and Prl-binding receptors (Prl-R) have b een described to share distinctive features with the members of the ne wly described cytokine/ hemopoietin receptor superfamily. Here we show that the hormone can functionally interact with lineage-specific hemo poietic factors. When highly purified progenitor cells (CD34+ve) were seeded in semisolid methylcellulose cultures in the presence of interl eukin (IL)-3, granulocyte-macrophage colony stimulating factor (CM-CSF ), and erythropoietin (Epo), a selective enhancing effect of Prl on th e formation of colony forming unit-granulocyte (CFU-C) and burst formi ng unit-erythroid (BFU-E) colonies was observed. The effect of the hor mone was plotted as a bell shaped curve, with the optimal response at the supraphysiological concentration of 50 ng/ml. Limiting dilution an alysis showed that Prl acted directly on hemopoietic progenitors. This was confirmed by the observation on the CD34+ve cells of Prl-binding sites reacting with the specific monoclonal antibodies (mAbs), U5 and PrR-7A. Immunoprecipitation of the metabolically labeled CD34+ve cells with the PrR-7A mAb revealed a structure of 43 kD under reducing cond itions. Analysis of the early events associated with the Prl/Prl-R int eraction showed an increased number of cells engaged in DNA and hemogl obin synthesis. Enhanced erythroid differentiation of CD34+ve cells in the presence of Prl was secondary to upmodulation of receptors for th e lineage-specific factor Epo. Together these data demonstrate the exi stence of a functional interplay between Prl and hemopoietic factors. (C) 1995 Wiley-Liss, Inc.