Luteotropic roles of prolactin in early pregnant hamsters

Prolactin (PRL) has long been regarded as a luteotropin maintaining early pregnancy in rodents. To delineate luteotropic roles of PRL in terms of luteal vascularization and immune privilege, luteal expression of Thy-1 differentiation protein, Fas, and Fas ligand (FasL) in early pregnancy was studied in hamsters on Day 4 of pregnancy (P4 group). Release of pituitary PRL was blocked by daily treatment with bromocriptine (1 mg s.c. given at 1000 h) on Days 1-4 of pregnancy (PB group). PRL withdrawal induced functional luteolysis, as evidenced by a precipitous drop in serum progesterone to background levels. In situ 3' end-labeling of fragmented DNA (TUNEL method) also clearly showed that many apoptotic nuclei accumulated in the disintegrated luteal vessels in the corpus luteum in the PB group. Immunohistochemical studies showed that luteal Thy-1-positive vascular pericytes were abundant in the P4 group but rare in the PB group. Thus, PRL is essential for luteal vascularization in early pregnancy. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction data showed that Fas protein and mRNA levels increased, whereas those of FasL decreased after PRL withdrawal. Accordingly, apoptosis initiated by Fas-FasL interaction is involved in the bromocriptine-induced luteolysis. Therefore, luteotropic roles of PRL are to support Thy-1 positive pericytes in maintaining proper luteal vascularization and to prevent immune insult by preserving a balance between luteal Fas and FasL expression in early pregnancy.