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Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and the Biological Psychiatry Branch, National Institute of Mental Health, Alcohol, Drug Abuse and Mental Health Administration Bethesda, Maryland 20892
the Holy Cross Hospital Silver Spring, Maryland 20291.
Address requests for reprints to: Dr. Andrew N. Margioris, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 9000 Rockville Pike, Bethesda, Maryland 20892.
Human placenta contains the POMC-derived peptides ACTH, aMSH, and β-endorphin, and CRH. High concentrations of immunoreactive (IR) CRH have been recently demonstrated in maternal plasma during pregnancy. To determine if the human placenta secretes CRH and POMC-derived peptides, we developed an in vitro human placental fragment perifusion system. The perifused tissue released IR-CRH and POMC-derived peptides at a constant rate for at least 5 h. The mean IR-CRH concentration in the effluent (under basal conditions) was 158 ± 26 (±SD) pg (34.5 ± 5.8 fmol)/5-min fraction·g tissue. IR-
MSH, IR-β-endorphin, and IR-ACTH were also released into the perifusion medium; the mean concentration of
MSH released was 24.6 ± 8 pg (14.8 ± 4.8 fmol)/fraction·g, that of ACTH was 2.9 ± 1.9 pg (0.65 ± 0.43 fmol)/fraction·g, and that of β-endorphin was 12.9 ± 6 pg (3.8 ± 1.7 fmol)/fraction·g. We examined the effects of human CRH, oxytocin, vasopressin, and dexamethasone on placental POMC peptide secretion. Five-minute pulses of 10–8 or 10–6 mol/L human CRH or oxytocin produced an immediate and dose-dependent increase in all POMC peptides in the effluent. A 5-min pulse of 10–8 or 10–6 mol/L vasopressin had no effect. A continuous 4-h exposure to 10–6 mol/L dexamethasone had no effect on either basal IR-CRH or POMC-derived peptide or their KCl-induced release. In conclusion, we found that 1) human placenta releases IR-CRH and POMC-derived peptides in vitro; this phenomenon seems to be independent of glucocorticoid control; 2) placental CRH may have a paracrine effect on placental POMC peptide release in addition to its possible action on maternal pituitary hormone release; and 3) oxytocin, but not vasopressin, stimulates placental POMC peptide release.
Received September 14, 1987.
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