Diprolene
Effect of maternal betamethasone administration at midgestation on baboon fetal adrenal gland development and adrenocorticotropin receptor messenger ribonucleic acid expression.

Aberdeen GW, Leavitt MG, Pepe GJ, Albrecht ED.

Department of Obstetrics/Gynecology/Reproductive Sciences, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore 21201, USA.

Although fetal pituitary ACTH is important to fetal adrenal growth and steroidogenesis in the second half of primate pregnancy, its role in adrenal development and function has not been established in vivo in the first half of gestation. In the present study, therefore, baboons were treated at midgestation with betamethasone to determine the effect of fetal pituitary ACTH on fetal adrenal growth, development, and ACTH receptor and P-450 enzyme messenger ribonucleic acid (mRNA) levels. The administration of betamethasone to baboon mothers on days 60-99 of gestation (term = 184 days) decreased fetal pituitary POMC mRNA levels by 54% (P < 0.01) and fetal serum ACTH levels to undetectable values (P < 0.05). The decline in ACTH was associated with decreases in fetal adrenal weight (P < 0.001), cortical cell size (P < 0.05), appearance of apoptosis and cellular disorganization, and a loss of immunocytochemically demonstrable definitive zone-specific delta5-3beta-hydroxysteroid dehydrogenase expression. The concomitant administration of ACTH and betamethasone restored these aspects of adrenal integrity to normal. Moreover, there was approximately a 95% decrease (P < 0.01) in fetal adrenal expression of ACTH receptor, P-450 cholesterol side-chain cleavage, and P-450 17alpha-hydroxylase 17/20-lyase mRNA levels after betamethasone administration. We conclude that fetal pituitary ACTH is necessary for the growth and development of fetal and definitive cortical zones and the marked coordinated increase in ACTH receptor and maintenance of P-450 cholesterol side-chain cleavage/P-450 17alpha-hydroxylase 17/20-lyase expression in the baboon fetal adrenal gland during the first half of gestation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9506759&dopt=Abstract betamethasone Diprolene AF



Diprolene
A single dose of antenatal betamethasone enhances isoprenaline and prostaglandin E2-induced relaxation of preterm ovine pulmonary arteries.

Gao Y, Tolsa JF, Shen H, Raj JU.

Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, Calif 90502, USA.

Beta-adrenergic agonists and prostaglandin E2 (PGE2) play an important role in perinatal pulmonary circulation. We have determined the effect of antenatal glucocorticoid treatment on isoprenaline- and PGE2-mediated relaxation of pulmonary arteries of newborn preterm lambs. Ovine fetuses (121 days of gestation; term = 150 days) received a single intramuscular dose of betamethasone (0.5 mg/kg) or saline. Fifteen hours after the injection, the lambs were delivered, ventilated for 3 h, and sacrificed. The fourth-generation pulmonary arteries were dissected and cut into rings for study. In endothelin-1-preconstricted vessels, isoprenaline, PGE2, and forskolin (an activator of adenylyl cyclase) induced greater relaxations of pulmonary arteries of betamethasone-treated lambs than those of controls. 8-Bromo-cyclic adenosine monophosphate, a cell membrane permeable analogue of cyclic adenosine monophosphate, caused similar relaxation of all vessels. When stimulated with isoprenaline and PGE2, the adenylyl cyclase activity of crude membrane preparations of pulmonary arteries treated with betamethasone was greater than that of controls. These results show that single-dose antenatal betamethasone treatment enhances relaxation of pulmonary arteries of preterm lambs induced by isoprenaline and PGE2 and that an enhanced adenylyl cyclase activity contributes to the effect of betamethasone on pulmonary arteries of preterm lambs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9535536&dopt=Abstract betamethasone Diprolene AF



Diprolene
Direct fetal glucocorticoid treatment alters postnatal adaptation in premature newborn baboons.

Ervin MG, Seidner SR, Leland MM, Ikegami M, Jobe AH.

Department of Obstetrics and Gynecology, University of California, Los Angeles School of Medicine, Harbor-UCLA Medical Center, Torrance 90502, USA.

Abnormalities of premature newborn adaptation after preterm birth result in significant perinatal mortality and morbidity. We assessed the effects of short-term (24 h) fetal betamethasone exposure on preterm newborn baboon pulmonary and cardiovascular regulation and renal sodium handling during the first 24 h after birth. Male fetal baboons (Papio) (124-day gestation, term 185 days) received ultrasound-guided intramuscular injections of saline (n = 5) or betamethasone (0.5 mg/kg; n = 5). Fetuses were cesarean delivered 24 h later, treated with 100 mg/kg surfactant, and ventilated by adjusting peak inspiratory pressures to maintain PCO2 values of 35-50 mmHg for 24 h. Betamethasone- vs. saline-treated mean +/- SE newborn body weights (0.45 +/- 0.02 vs. 0.41 +/- 0.01 kg) were similar. Although prenatal betamethasone did not affect postnatal lung function (PCO2, arterial/alveolar O2 gradient, or dynamic compliance), plasma hormone (cortisol or thyroxine), or catecholamine levels, mean arterial pressure (25 +/- 1 vs. 32 +/- 1 mmHg), plasma sodium concentration (132 +/- 2 vs. 138 +/- 1 meq/l), glomerular filtration rate (0.07 +/- 0.02 vs. 0.16 +/- 0.02 ml.min-1.kg-1), and renal total sodium reabsorption (1.5 +/- 0.5 vs. 16.0 +/- 3.0 mu eq.min-1.kg-1) values were significantly lower in saline-treated than in betamethasone-treated newborns at 24 h. We conclude that despite the fact that there are no pulmonary and endocrine effects, antenatal glucocorticoid exposure alters premature newborn baboon vascular and renal glomerular function and improves sodium reabsorption after preterm delivery.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9575985&dopt=Abstract betamethasone Diprolene AF



Diprolene
Effect of betamethasone in vivo on placental corticotropin-releasing hormone in human pregnancy.

Marinoni E, Korebrits C, Di Iorio R, Cosmi EV, Challis JR.

2nd Department of Obstetrics and Gynecology, University La Sapienza, Rome, Italy.

OBJECTIVE: The objective was to determine the effects of in vivo administration of prenatal betamethasone in patients at 26 to 35 weeks' gestation on corticotropin-releasing hormone concentrations in maternal and fetal plasma and amniotic fluid, and on corticotropin-releasing hormone localization in placenta and fetal membranes. STUDY DESIGN: A total of 49 pregnant women at risk for preterm delivery between 26 and 35 weeks' gestation were studied. Twenty-six patients received betamethasone (12 mg intramuscularly) for stimulation of fetal lung maturity. Cord blood, amniotic fluid, placental tissue, and fetal membranes were obtained from 22 of these patients at delivery by elective cesarean section at 33.8+/-2.4 weeks' gestation. In control patients (n=23) at comparable gestational age, blood samples were taken for hormone analysis (n=8), and cord blood, amniotic fluid, and tissues were collected at elective cesarean section at 34.1+/-2.3 weeks' gestation. Concentrations of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol were determined by radioimmunoassay. Localization of tissue immunoreactive corticotropin-releasing hormone was assessed by immunohistochemistry. RESULTS: Betamethasone caused approximately 90% reduction in maternal cortisol and 50% reduction in maternal plasma adrenocorticotropic hormone. In patients at >30 weeks' gestation, there was a significant increase in maternal plasma corticotropin-releasing hormone concentrations after betamethasone; maternal corticotropin-releasing hormone was not altered significantly in untreated patients. Corticotropin-releasing hormone levels were raised in umbilical cord blood by 48 hours and in amniotic fluid 1 week after betamethasone administration. There was increased immunohistochemical staining for corticotropin-releasing hormone in placental syncytiotrophoblast and in fetal membranes of patients treated with betamethasone. CONCLUSIONS: These studies provide the first evidence for in vivo stimulation of plasma corticotropin-releasing hormone, likely of placental origin, by glucocorticoids in third trimester human pregnancy. The results suggest that increases in endogenous cortisol during normal gestation may contribute to placental corticotropin-releasing hormone output and to the rise in maternal plasma corticotropin-releasing hormone concentrations during late pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9579442&dopt=Abstract betamethasone Diprolene AF



Diprolene
The effect of epidural injection of betamethasone or bupivacaine in a rat model of lumbar radiculopathy.

Hayashi N, Weinstein JN, Meller ST, Lee HM, Spratt KF, Gebhart GF.

Department of Orthopedic Surgery, Wakayama Medical College, Japan.

STUDY DESIGN: The effect of epidural injection of betamethasone or bupivacaine was investigated in an animal model of lumbar radiculopathy. OBJECTIVE: To investigate the effects of an epidural steroid (betamethasone) or a local anesthetic (bupivacaine) in an animal model of radiculopathy produced by nerve root irritation. SUMMARY OF BACKGROUND DATA: Epidural injections are commonly used for the treatment of low back pain and sciatica. However, efficacy remains controversial, and there is a paucity of basic information to support clinical use or the injections. METHODS: Fifty-one rats were used. The left L4 and L5 nerve roots were loosely ligated with chromic gut, and either betamethasone, bupivacaine, betamethasone in combination with bupivacaine, or saline was injected using an epidurally placed catheter. The effects of epidural injection were evaluated using response to noxious stimuli and immunohistochemical methods. RESULTS: In betamethasone-treated rats (either alone or in combination with bupivacaine), thermal hyperalgesia was significantly less (P < 0.010 after surgery than that in saline- or bupivacaine-treated groups, in which the hyperalgesia was maximum at 2-3 postoperative weeks before resolving 5 weeks after surgery. Immunohistochemical analysis did not correlate with these results. CONCLUSIONS: Epidural steroid injection has a significant effect on the thermal hyperalgesia produced in a model of radiculopathy, which may provide clinical support for advocates of epidural steroids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9580954&dopt=Abstract betamethasone Diprolene AF