Administration of unmodified prolactin (U-PRL) and a molecular mimic of phosphorylated prolactin (PP-PRL) during rat pregnancy provides evidence thatthe U-PRL : PP-PRL ratio is crucial to the normal development of pup tissues

During rat pregnancy initial high concentrations of prolactin (PRL) decline by about day 9, concomitant with an increase in the ratio of unmodified to phosphorylated PRL. The physiological significance of both the decline in total PRL and the change in ratio of the two PRLs is unknown. To test the i mportant of each, either unmodified PRL (U-PRL) or a molecular mimic of pho sphorylated PRL (PP-PRL) were continuously administered to rats throughout pregnancy. A dose of 6 mug/24 h resulted in circulating concentrations of 5 0 ng/ml of each administered PRL and had little effect oil the pregnancy it self. After birth, pups were killed and various tissues examined. III the p up lungs, exposure to additional PP-PRL caused a reduction in epithelial in tegrity and an increase in apoptosis, whereas exposure to additional U-PRL had beneficial, anti-apoptotic effects. In the heart, PP-PRL caused an appa l-ent developmental delay, whereas U-PRL promoted tissue compaction. In the blood, U-PRL increased the number of mature red blood cells at the expense of white blood cell production. Within the white blood cell population, my elopoiesis was favored at the expense of lymphopoiesis. PP-PRL, in contrast , had a less dramatic influence on the hematopoietic compartment by promoti ng red blood cell maturation and granulocyte production. In the thymus, exp osure to PP-PRL caused accumulation of apoptotic thymocytes in enlarged gla nds, whereas exposure to U-PRL resulted in smaller thymi. In the spleen, ex posure to U-PRL increased cellularity, with the majority of cells belonging to the erythroid series - a finding consistent with increased red blood ce lls in the circulation. Exposure to PP-PRL was without discernible effect. In all of these tissues, the contrasting effects of the two PRLs indicate t hat the absolute concentration of PRL is not crucial, but that the ratio of U-PRL to PP-PRL has a profound effect on tissue development. In brown fit, both PRL preparations decreased the number of lipid droplets. This result is therefore probably a consequence of the increase in total PRL. The resul ts of this study attest to the importance of the U-PRL:PP-PRL ratio normall y present during pregnancy and have provided clues as to the possible patho genesis of a variety of neonatal problems.