Hypothesis to be Tested: """"""""The placental luteinizing-hormone releasing hormone (LRH) receptor serves a role in the control of placental production of human chorionic gonadotrpin (hCG), and the receptor concentration itself is modulated by one or more steroids from the fetal adrenal."""""""" If hCG stimulates steroidogenesis by the fetal adrenal, the hypothesis completes a negative feedback control system interrelating production of placental hCG, estradiol, and progesterone: HCG stimulates fetal adrenal on steroid production and one or more adrenal steroids inhibit hCG production by reducing the concentration of the LRH receptor. Estradiol production is controlled by availability of the adrenal androgen aromatase substrates. Placental progesteron production may be modulated as well since adrostenedione is an inhibitor of placental 3b-hydroxysteroid-dehydrogenase. The proposal will test this hypothesis in the human by two modes of investigation: 1) In vitro studies of placental explants during 6 days in culture to test the effects of steroid hormones, LRH, LRH analog, fetal calf serum, and oxygen partial pressure on the LRH receptor and the hCG response to LRH and dibutyryl adenosine 3 feet,5 feet-monophosphate (dbcAMP). 2) Multiple linear regression analysis of in vivro placental LRH content, LRH receptor concentration, and concentrations of hCG and steroid hormones in both maternal and cord blood obtained at 8-16 weeks and at term. Two of the 4 steroid hormons to be determined in part 2) will be chosen based on the results of the experiments outlined in part 1). The other 2 steroids will be dehydro-epiandrosterone sulfate and testosterone. All hormone determinations will be performed by radioimmunoassay. The LRH receptor will be determine utilizing a 125I-LRH analog. Since placental hormones (including prostaglandins) are important in multiple aspects of pregnancy, the long term goals to which this proposal is pertinent are as follows: to understand fully the endocrinology of the feto-placental unit and the physiology of initiation of parturition in order to improve diagnostic and therapeutic capabilities during pregnancy. These goals are pertinent generally to improving the health care of pregnant women and specifically to management and treatment of premature labor, post maturity, pre-eclampsia, and abnormalities of lactation.
| Haning Jr, R V; Curet, L B; Poole, W K et al. (1989) Effects of fetal sex and dexamethasone on preterm maternal serum concentrations of human chorionic gonadotropin, progesterone, estrone, estradiol, and estriol. Am J Obstet Gynecol 161:1549-53 |
| Haning Jr, R V; Breault, P H; DeSilva, M V et al. (1988) Effects of fetal sex, stage of gestation, dibutyryl cyclic adenosine monophosphate, and gonadotropin releasing hormone on secretion of human chorionic gonadotropin by placental explants in vitro. Am J Obstet Gynecol 159:1332-7 |
