THE MATERNAL HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN THE 3RD TRIMESTEROF HUMAN-PREGNANCY

OBJECTIVE The third trimester of pregnancy is characterized by a mildl y hyperactive hypothalamic-pituitary-adrenal (HPA) axis, possibly driv en by elevated circulating levels of corticotrophin releasing hormone (CRH) of placental origin. In-vitro studies have demonstrated that glu cocorticoids and oestrogen stimulate while progesterone inhibits the e xpression of CRH mRNA and/or protein, suggesting that several potentia l interactions between the placenta and the HPA axis may exist. DESIGN AND PATIENTS To investigate the detailed pattern of circulating immun oreactive (ir) CRH, ACTH, cortisol, oestradiol and progesterone during the third trimester of pregnancy, plasma samples were drawn serially every 30 minutes from 22 healthy pregnant women (age 32.0 +/- 1.1 year s, mean +/- SE) between the 34th and 36th week of gestation. Ten women had plasma samples drawn between 0800 h and 2000 h (daytime group), a nd 12 between 2000 h and 0300 h (night-time group). The hormone concen trations obtained were analysed for pulsatility by the Detect program, for detection of circadian rhythmicity by comparison between the firs t and second 6-hour periods within each group by Student's t-test, and for time-dependent correlations by cross-correlation analysis. RESULT S All five hormones were secreted in a pulsatile fashion. There was no apparent circadian rhythm of CRH or oestradiol secretion, whereas the re was a clear circadian rhythm in plasma ACTH, cortisol and progester one secretion, with the latter in reverse phase (P<0.05). No significa nt correlations were observed between CRH and ACTH, whereas, as expect ed, ACTH and cortisol concentrations were strongly correlated with eac h other over time (r = 0.32 and 0.70 at lag time 30 minutes for the da ytime and night-time groups, respectively), with ACTH leading cortisol . A weak positive correlation was observed between CRH and cortisol co ncentrations for the night-time group at lag time 0 minute, suggesting that the latter may have a positive effect on the former in vivo. CON CLUSIONS These data suggest that placental CRH, although pulsatile, dr ives quantitatively the maternal HPA axis in the third trimester of pr egnancy in a non-circadian, non-pulsatile fashion. The maternal HPA ax is is probably driven in a circadian and pulsatile fashion by another major ACTH secretagogue, most likely AVP of parvocellular paraventricu lar nucleus origin.