Corticotropin-releasing hormone and oxytocin stimulate the release of placental proopiomelanocortin peptides.
Human placenta contains the POMC-derived peptides ACTH, alpha MSH, and beta-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-alpha MSH, IR-beta-endorphin, and IR-ACTH were also released into the perifusion medium; the mean concentration of alpha 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 beta-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.
Margioris
A N
AN
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Grino
M
M
Protos
P
P
Gold
P W
PW
Chrousos
G P
GP
D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000378:metabolism*; D002850:Chromatography, Gel; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D010121:Oxytocin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D010920:Placenta / Q000032:analysis / Q000187:drug effects*; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D013268:Stimulation, Chemical; D000521:alpha-MSH / Q000032:analysis / Q000378:metabolism*; D001615:beta-Endorphin / Q000032:analysis / Q000378:metabolism*
D010446:Peptide Fragments; C048786:pro-opiomelanocortin human joining peptide(77-109); D010121:Oxytocin; D000521:alpha-MSH; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone