The overall objective is to learn as much as possible about the control and dynamics of ovarian hormone production during pregnancy, particularly during the period of transition from pituitary to placental regulation of ovarian function. Other than progesterone (P) and estradiol (E2), the major ovarian steroid in which we are interested is testosterone (T), as a consequence of our earlier demonstration of a midpregnancy androgen surge which varies in magnitude in strains of mice that differ in reproductive performance. The immediate objectives are grouped into three areas: androgen and pregnancy, genetic variation in endocrine function, and estrogen activity in the female mouse. In the area of androgen during pregnancy, we will determine the source, regulation and function of the midpregnancy testosterone surge. The site(s) of ovarian T production (luteal and/or nonluteal) will be ascertained using in vitro and in vivo techniques; the relative roles of pituitary and placental hormones in the control of T secretion will be assessed in pregnant and psuedopregnant mice subjected to hypophysectomy and/or hysterectomy or bearing decidual as compared to trophoblastic tissues; the function of the midpregnancy T surge will be investigated by inhibiting T biosynthesis, by using androgen antogonists, and by performing endocrine ablation and steroid replacement experiments. Studies on genetic variation in endocrine function are directed toward elucidating the basis of strain differences in steroid secretion and toward exposing the rate-limiting factors in androgen production. Using mice selected for various traits, we will examine ovarian responsiveness to gonadotropic stimulation and ovarian enzyme activities in strains with naturally-occurring high, intermediate and low T levels. We will also use embryo transfer to partition maternal from placental-fetal effects on steroid production during pregnancy. In the area of estrogen activity, we will isolate and define as yet unidentified components of plasma and urine which have demonstrated estrogen-like immuno- and biopotency. The physiological significance of these unknown compounds will be determined as well as their relationship to estradiol.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD000394-22
Application #
3310064
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1977-09-01
Project End
1989-03-31
Budget Start
1985-12-01
Budget End
1989-03-31
Support Year
22
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Earth Sciences/Resources
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Barkley, M S; FitzGerald, R (1990) Influence of embryonic and maternal genotype on gestational events in the mouse. J Reprod Fertil 89:285-91
Barkley, M (1990) Evidence for maternal regulation of progesterone production at midpregnancy in the mouse. Proc Soc Exp Biol Med 194:64-8
DeLeon, D D; Zelinski-Wooten, M B; Barkley, M S (1990) Hormonal basis of variation in oestrous cyclicity in selected strains of mice. J Reprod Fertil 89:117-26
Spearow, J L (1986) Changes in the kinetics of follicular growth in response to selection for large litter size in mice. Biol Reprod 35:1175-86
Thompson, M A; Lasley, B L; Barkley, M S et al. (1985) HPLC separation of anti-estrogen and estrogen receptor binding components of mouse plasma. Steroids 46:609-18
Barkley, M S; Lasley, B L; Thompson, M A et al. (1985) Equol: a contributor to enigmatic immunoassay measurements of estrogen. Steroids 46:587-608