The overall goal of the proposed studies is to better define the relative contributions of pathways that provide cholesterol precursor for P4 production during primate gestation. The proposed studies will utilize the baboon as the model for study of the endocrinology of human pregnancy. Three major experiments are proposed. In the first series of experiments, the relative contributions of pathways that provide cholesterol precursor for placental P4 biosynthesis will be studied during normal gestation. Baboons will also be treated after administration of an inhibitor of hepatic lipoprotein secretion 4-aminopyrazolo [3-4-d]pyrimidine (4-APP). mRNA concentrations for LDL, acLDL receptors, and LDL receptor-related protein (LRP) will be assessed by RT-PCR. The resultant proteins synthesized will be quantitated by Western blots and key enzymes that regulate de novo cholesterol synthesis will be quantitated by radioenzymatic techniques. The second series of experiments will examine the influence of estrogen on the cholesterol pathway. Placental LDL uptake will be inhibited by 4-APP and elimination of the stimulatory effect of estrogen by removal of fetal androgen precursors after fetectomy. The last series of experiments will examine the capacity of the corpus luteum for P4 biosynthesis after fetectomy and or 4-APP treatment. The knowledge gained from these experiments will provide an increased understanding of the important physiologic events underlying the P4 mediated maintenance of pregnancy and the initiation of normal labor in the primate.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29HD032502-01A1
Application #
2205618
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1995-09-05
Project End
1999-08-31
Budget Start
1995-09-05
Budget End
1996-08-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Tulane University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Shi, Wenliang; Swan, Kenneth F; Henson, Michael C (2003) Expression of placental low-density lipoprotein receptor-related protein and scavenger receptors AI/AII transcripts in the baboon. Am J Obstet Gynecol 188:1211-2
O'Neil, J S; Green, A E; Edwards, D E et al. (2001) Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy. J Clin Endocrinol Metab 86:2518-24
Green, A E; O'Neil, J S; Swan, K F et al. (2000) Leptin receptor transcripts are constitutively expressed in placenta and adipose tissue with advancing baboon pregnancy. Proc Soc Exp Biol Med 223:362-6
Shi, W; Swan, K F; Lear, S R et al. (1999) Regulation of pathways determining cholesterol availability in the baboon placenta with advancing gestation. Biol Reprod 61:1499-505
Henson, M C; Castracane, V D; O'Neil, J S et al. (1999) Serum leptin concentrations and expression of leptin transcripts in placental trophoblast with advancing baboon pregnancy. J Clin Endocrinol Metab 84:2543-9
Jolibois Jr, L S; Shi, W; George, W J et al. (1999) Cadmium accumulation and effects on progesterone release by cultured human trophoblast cells. Reprod Toxicol 13:215-21
Jolibois Jr, L S; Burow, M E; Swan, K F et al. (1999) Effects of cadmium cell viability, trophoblastic development, and expression of low density lipoprotein receptor transcripts in cultured human placental cells. Reprod Toxicol 13:473-80
Henson, M C; Swan, K F; O'Neil, J S (1998) Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term. Obstet Gynecol 92:1020-8
Henson, M C (1998) Pregnancy maintenance and the regulation of placental progesterone biosynthesis in the baboon. Hum Reprod Update 4:389-405
Henson, M C; Greene, S J; Reggio, B C et al. (1997) Effects of reduced maternal lipoprotein-cholesterol availability on placental progesterone biosynthesis in the baboon. Endocrinology 138:1385-91