Although temporally related to the near term fall in progesterone (Pr) and rise in estradiol (E2) observed in the pregnant rat, the hormonal control for the loss of beta adrenergic responsiveness and modulation of beta-2 adrenergic receptor (B2AR) signal transduction events observed near term in the pregnant rat are unknown at this time. The proposed experiments will test the hypothesis that E2 and/or Pr regulate beta-2 adrenergic responsiveness by directly effecting B2AR expression and/or B2AR signal transduction mechanisms. This hypothesis will be tested in a systematic fashion using rat myometrial tissue obtained during normal gestation, myometrial tissue obtained from pregnant rats undergoing steroid hormone manipulation in vivo, and cultured rat uterine myocytes directly stimulated in vitro with steroid hormones. This revised, competitive renewal research grant application is to evaluate the effects of gestation and steroid hormones on: 1) the expression of myometrial beta-2 adrenergic receptors utilizing radioligand binding studies and Northern blots, 2) guanine nucleotide regulatory protein (Gs) function, Gs-alpha subunit MRNA levels, and protein expression, 3) adenylate cyclase (AC) activity, AC MRNA levels, and protein expression, and 4) protein kinase A (CAMP-dependent protein kinase) activity, myocyte PKA target peptides, PKA MRNA levels, and protein expression. The proposed studies will further characterize adrenergic signal transduction mechanisms in pregnant myometrial tissue, with particular emphasis on the elucidation of those events regulated by these steroid hormones as parturition approaches.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD022063-05A3
Application #
3321362
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1987-06-01
Project End
1996-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Phillippe, M; Saunders, T; Basa, A (1997) Intracellular mechanisms underlying prostaglandin F2alpha-stimulated phasic myometrial contractions. Am J Physiol 273:E665-73
Phillippe, M; Basa, A (1997) Effects of sodium and calcium channel blockade on cytosolic calcium oscillations and phasic contractions of myometrial tissue. J Soc Gynecol Investig 4:72-7
Harris, C M; Saunders, T; Baunoch, D A et al. (1997) Gq-protein alpha subunit expression and distribution in pregnant rat myometrial tissues. J Soc Gynecol Investig 4:209-17
Principe, D; Sanseverino, M; Saunders, T et al. (1997) Beta-adrenergic receptor subtype gene expression in timed-pregnant rat myometrium. Am J Obstet Gynecol 176:349-57
Chien, E K; Tokuyama, Y; Rouard, M et al. (1997) Identification of gestationally regulated genes in rat myometrium by use of messenger ribonucleic acid differential display. Am J Obstet Gynecol 177:645-52
Chien, E K; Saunders, T; Phillippe, M (1996) The mechanisms underlying Bay K 8644-stimulated phasic myometrial contractions. J Soc Gynecol Investig 3:106-12
Phillippe, M; Chien, E M; Freij, M et al. (1995) Ionomycin-stimulated phasic myometrial contractions. Am J Physiol 269:E779-85
Phillippe, M (1995) The effects of thimerosal, a sulfhydryl reagent, on phasic myometrial contractions. Biochem Biophys Res Commun 211:1-6
Phillippe, M; Chien, E K (1995) Potassium chloride effects on the hormonal signal transduction mechanisms underlying phasic myometrial contractions. J Endocrinol 146:485-93

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