Estradiol implants in the arcuate nucleus induce lactogenesis in virgin rats. Role of progesterone

The aim of this study was to determine the effect of the centrally administered estradiol, and the effects of the consequent hypersecretion of prolactin (PRL) and progesterone, on lactogenesis as evaluated by mammary accumulation of casein and lactose. Bilateral cannulae containing 17beta-estradiol or cholesterol were implanted in the arcuate nucleus of virgin rats on the day of estrus (Day 0). In the first experiment different groups of rats were killed on Days 6, 9, 15, 17, or 19. Trunk blood was collected and abdominal mammary glands were taken. In the second experiment, estradiol-implanted rats received the progesterone antagonist mifepristone or vehicle at 14.00 h on Day 8 or 16 post-implant, and were killed 28 or 48 h later. Serum PRL and progesterone and mammary casein were measured by RIA and lactose was determined by an enzymatic assay. Estradiol-implanted rats showed a significant increase in both milk components at all time points after implant compared to controls. On Day 9 after estradiol implant, mifepristone had no effect on mammary content of casein or lactose. By contrast, on Day 16, mifepristone markedly increased both casein and lactose contents without modifying serum PRL and progesterone concentrations. In conclusion, 17beta-estradiol implants in the arcuate nucleus of virgin rats results in hyperprolactinaemia and stimulates mammary accumulation of casein and lactose in the absence of feto-placental units. Despite the prolonged luteal activation, the sustained high levels of circulating progesterone become inhibitory to lactogenesis after a relatively long period after implant.