ABSTRACT
Parathyroid hormone-related protein (PTHrP), a oncofetal gene product possessing smooth muscle relaxant properties, has been found in rat and human uterine smooth muscle cells (USMC) where it is postulated to regulate myometrial tone and/or blood flow. Studies investigating the gestational regulation of PTHrP in human USMC have not been performed. This study was conducted to determine if pregnancy alters the capacity of USMC to secrete or respond to PTHrP. USMC cultures were established from 8 hysterectomy specimens (H) and 7 non-laboring (NP) and 5 laboring term pregnant uterine biopsies (LP). PTHrP secretion was measured at baseline and in response to TGF-beta1 using a immunoradiometric assay. The USMC response to PTHrP was assessed by incubating cultures with human (1-34)PTHrP and measuring cellular cAMP by radioimmunoassay. We found that cultures from the groups did not differ with respect to basal PTHrP secretion. TGF-beta1, on the other hand, produced dose-dependent increases in secreted PTHrP in each group such that LP>NP>H at 12 hrs and LP>NP and H 24 hrs. Maximal responses were found at 24 hrs in cells treated with 10 ng/ml TGF-beta1 (LP: 2034+/-366 vs NP: 1485+/-427; H: 1250+/-202 fmol/mg). Incubation of cultures with PTHrP produced dose-dependent increases in cAMP production, with 10(-7) M increasing levels by 64%. Neither pregnancy nor labor significantly affected the cAMP response. These findings indicate that the human myometrium has the capacity to increase PTHrP secretion during pregnancy and labor through a TGF-beta-dependent pathway. Such findings are consistent with a role of PTHrP in enhancing uterine blood flow.
Subject(s)
Labor, Obstetric/metabolism , Myometrium/metabolism , Parathyroid Hormone/metabolism , Pregnancy/metabolism , Proteins/metabolism , Adult , Cells, Cultured , Cyclic AMP/metabolism , Dose-Response Relationship, Drug , Estradiol/pharmacology , Female , Humans , Isoproterenol/pharmacology , Myometrium/cytology , Myometrium/drug effects , Parathyroid Hormone-Related Protein , Transforming Growth Factor beta/pharmacologyABSTRACT
OBJECTIVE: To determine whether betamethasone administered to women at risk of preterm delivery causes adrenal suppression. METHODS: Ten women at risk of preterm delivery had three weekly low-dose (1 microg) ACTH stimulation tests with the first one between 24 and 25 weeks' gestation. Immediately after the first and second ACTH stimulation tests, we gave each woman a 12-mg betamethasone dose intramuscularly and repeated it 24 hours later. The third ACTH stimulation test was 1 week after the second course of betamethasone. Serum cortisol levels were measured before (baseline) and 30 minutes after ACTH administration. RESULTS: All subjects had normal baseline and stimulated cortisol levels for the first ACTH stimulation test. Mean baseline serum cortisol levels decreased with each ACTH stimulation test, from 25.4 +/- 4.8 microg/dL (before betamethasone) to 4.3 +/- 4.0 microg/dL (1 week after the second course of betamethasone) (P <.001). The mean stimulated cortisol levels also decreased from 33.0 +/- 4.3 microg/dL (before betamethasone) to 11.8 +/- 6.4 microg/dL (1 week after the second course of betamethasone) (P <.001). Compared with initial ACTH stimulation tests, laboratory evidence of adrenal suppression occurred in four patients 1 week after the first course of betamethasone and in seven patients after the second course. No signs or symptoms of Addisonian crisis occurred antepartum or intrapartum. CONCLUSION: Antenatal administration of betamethasone produced measurable adrenal suppression in women at risk of preterm delivery. The number of women with adrenal suppression increased each week that antenatal betamethasone was repeated. (Obstet Gynecol 2000;96:287-90.)
