ROLE OF PLACENTAL LACTOGENS IN PREGNANCY

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The mouse conceptus produces two lactogenic hormones, placental lactogen (PL) and midpregnancy lactogen. The objectives of this proposal are (1) to study the regulation of secretion of PL and (2) to examine the biological activities of PL and midpregnancy lactogen and two other lactogenic hormones, prolactin (PRL) and growth hormone (GH), in several target tissues. Regulation of PL secretion by the pituitary, ovaries, fetus and decidua and by growth factors will be studied. In addition, the influence of genetic factors on mPL secretion will be examined. A system for primary culture of placental trophoblast giant cells in serum-free medium will be established and the effects of various hormones and growth factors on mPL secretion and on cell growth will be examined. PL, midpregnancy lactogen, PRL and GH are all present during pregnancy in the mouse. The effects of each of these hormones on target tissues will be studied to assess the relative potencies of the hormones in each tissue and to determine whether tissues at different stages of pregnancy respond preferentially to some of the hormones. The effects of these hormones on mammary gland casein, Alpha-lactalbumin and fatty acid synthesis will be determined. The ability of these hormones to stimulate mammary gland epithelial cell growth and to bind to mammary gland receptors will be evaluated. The effects of these hormones on somatomedin produced by maternal and fetal liver will be studied. The ability of these hormones to stimulate fetal growth will be assessed. The studies proposed in this application will be carried out with hormones purified from the mouse to study the endocrinology or pregnancy in the mouse. Thus the results of these studies will not be subject to problems of interpreting data collected from heterologous systems. PL is present in humans and serum PL levels have been used as one index of fetal well-being. The studies in this proposal will provide information about the physiology of this hormone and the interaction of this hormone with other hormones with similar activities during pregnancy in an animal model. The information obtained from studies in this animal model may prove relevant to the human.