Immunoreactive Corticotropin-Releasing Hormone in Human Plasma During Pregnancy, Labor, and Delivery*

Abstract

We previously reported that immunoreactive corticotropin-releasing hormone (CRH) is present in human placenta and third trimester maternal plasma, and that such material is very similar to rat CRH and the predicted structure of human CRH. We suggested that maternal plasma immunoreactive CRH may be of placental origin. To further investigate this possibility, we measured plasma immunoreactive CRH in women during pregnancy, labor, and delivery and 1 and 2 h postpartum, and in nonpregnant women. Umbilical cord plasma and placental CRH concentrations were also measured. In the first trimester of pregnancy, the mean maternal plasma level was 5.9 +/- 1.0 pg (+/- SEM)/ml (n = 24), not significantly different from that in 10 nonpregnant women (5.8 +/- 0.8 pg/ml). Plasma CRH concentrations progressively increased during pregnancy (second trimester, 35.4 +/- 5.9 pg/ml (n = 39); early third trimester (28-34 weeks), 263 +/- 41 pg/ml (n = 14); late third trimester (35-40 weeks), 800 +/- 163 pg/ml (n = 20)]. There was a significant correlation between maternal plasma CRH levels and weeks of pregnancy. Plasma CRH concentrations were further elevated (2215 +/- 329 pg/ml; n = 9). During early labor, peaked at delivery (4409 +/- 591 pg/ml; n = 28), and declined rapidly after delivery [1 h postpartum, 1042 +/- (353 pg/ml (n = 13); 2 h postpartum, 346 +/- 91 pg/ml (n = 13)]. There was a significant correlation (r = 0.562; P less than 0.01) between matched maternal plasma and placental CRH concentrations. The mean umbilical cord plasma CRH level (50.6 +/- 6.1 pg/ml; n = 28) was much lower than that in the mother at the time of delivery. Umbilical venous plasma CRH levels were significantly greater than those in simultaneously obtained umbilical arterial plasma (70.8 +/- 11.3 and 41.8 +/- 4.9 pg/ml, respectively; n = 11). There was a significant correlation (r = 0.384; P less than 0.05) between maternal and fetal CRH concentrations. Gel filtration of plasma obtained from women during the third trimester, at delivery, and early postpartum and placental extracts revealed two major peaks of immunoreactive CRH: a high mol wt peak and one at the elution position of rat CRH. In contrast, only rat CRH-sized material was detected in plasma from nonpregnant women and umbilical cord plasma. Maternal plasma immunoreactive CRH-sized material stimulated ACTH release from anterior pituitary tissue in a dose-dependent manner and was equipotent with rat CRH.(ABSTRACT TRUNCATED AT 400 WORDS)

Lack of Correlation Between Immunoreactive Corticotropin‐Releasing Factor Concentration Profiles in Hypophysial‐Portal and Peripheral Plasma

“…This strongly suggested an alternative, non-hypothalamic origin of irCRF-41 present in the systemic circulation. Multiple sources of peripheral irCRF-41 may be Postulated on the basis of immunohistochemical or content studies (18)(19)(20)(21)(22)(23)(24). Of particular interest were the adrenal glands, which contain and secrete CRF-like immunoreactivity (23,24).…”

“…Several laboratories have reported the presence of irCRF-41 in human or rat peripheral plasma (10)(11)(12)(13)(14)(15)(16)(17). During pregnancy, peripheral irCRF-41 appears to be derived from the placenta (18)(19)(20). The source of peripheral irCRF-41 in non-pregnant animals is unknown and it has been postulated that it may reflect, at least in part, hypothalamic irCRF-41 secretion (13,14,16,17); other sources include the gastrointestinal tract (21), the pancreas (22) and the adrenal gland (23,24).…”

Large Molecular Weight Immunoreactive Corticotrophin‐Releasing Hormone has Bioactivity on Superfused Ovine Pituitary Cells

“…Human pregnancy is associated with increasing concentrations of plasma corticotrophin-releasing hormone immunoreactivity (CRH-IR) with gestational age (1)(2)(3)(4)(5)(6). It has been shown that the hormone, first isolated in ovine hypothalami (7) and responsible for the release of adrenocorticotrophin (ACTH), /?-endorphin (PEP) and related peptides from the anterior pituitary (7), is present in human placental extracts (1)(2)(3).…”

“…It has been shown that the hormone, first isolated in ovine hypothalami (7) and responsible for the release of adrenocorticotrophin (ACTH), /?-endorphin (PEP) and related peptides from the anterior pituitary (7), is present in human placental extracts (1)(2)(3). The discovery of messenger RNA transcripts in the human placenta (8) and the demonstration of bioactive placental CRH-IR (1) and its release from placental cells in vitro (8,9) indicate placental synthesis and secretion of the peptide.…”

“…With the discovery of a specific CRH binding protein in the human blood circulation (lo), it has been postulated that the elevated CRH-1R during pregnancy is proteinbound and not bioactive, to account for an absence of a significant elevation of plasma ACTH during pregnancy (1 1). Multiple molecular weight forms of CRH-IR have been found in human placental extracts and blood plasma of pregnant women (2)(3)(4), but the nature of these forms, whether they are protein-bound forms of CRH-IR, artefacts of extraction/assay, or precursors, is uncertain.…”