Objectives: To evaluate calcium-regulating hormones and parathyroid hormone-related peptide (PTHrP) in normal human pregnancy and postpartum in women not deficient in vitamin D. Design: A prospective longitudinal study was conducted in pregnant Saudi women during the course of pregnancy (n ¼ 40), at term and 6 weeks postpartum (n ¼ 18). Maternal concentrations of serum calcidiol and calcitriol were determined, together with those of serum intact-parathyroid hormone (PTH), PTHrP, calcitonin, osteocalcin, human placental lactogen (hPL), prolactin, vitamin D binding protein, alkaline phosphatase, calcium, phosphate and magnesium. A group of non-pregnant women (n ¼ 280) were included for comparative purposes. Results: The calcidiol concentrations decreased (meanϮS.D.) significantly from 54Ϯ10 nmol/l in the first trimester to 33Ϯ8 nmol/l in the third trimester (P < 0:001) and remained decreased at term and postpartum (both P < 0:001). The calcitriol concentration increased through pregnancy, from 69Ϯ17 pmol/l in the first trimester to 333Ϯ83 pmol/l at term (P < 0:001). Intact-PTH concentrations increased from 1.31Ϯ0.25 pmol/l in the first trimester to 2.26Ϯ0.39 pmol/l in the second trimester, but then declined to values of the first trimester and increased significantly postpartum (4.02Ϯ0.36 pmol/l) (P < 0:001). PTHrP concentration increased through pregnancy from 0.81Ϯ0.12 pmol/l in the first trimester to 2.01Ϯ0.22 pmol/l at term and continued its increase postpartum (2.63Ϯ0.15 pmol/l) (P < 0:001). Significant positive correlations were evident between PTHrP and alkaline phosphatase up to term (r ¼ 0:051, P < 0:001) and between PTHrP and calcitriol (r ¼ 0:46, P < 0:001), osteocalcin (r ¼ 0:23, P < 0:05) and prolactin (r ¼ 0:41, P < 0:05) during pregnancy. Osteocalcin started to increase from 0.13Ϯ0.01 nmol/l in the second trimester, through pregnancy and postpartum (P < 0:001). Calcitonin was increased more than twofold by the second trimester compared with the first trimester (P < 0:001) and subsequently decreased (P < 0:001). Prolactin concentrations were significantly greater in the second (6724Ϯ1459 pmol/l) and third (8394Ϯ2086 pmol/l) trimesters compared with values before pregnancy (P < 0:001). hPL increased throughout the course of pregnancy, reaching a maximum at term (7.61Ϯ2.57 mIU/ml). There was no direct correlation between serum calcitriol concentrations during pregnancy and serum prolactin (r ¼ ¹0:12, P < 0:19) or serum hPL (r ¼ 0:17, P < 0:21). Significant changes were observed in the serum concentrations of calcium and phosphate, but not in that of magnesium, during the course of pregnancy; calcium concentrations showed a maximal decrease at term. Conclusions: Changes in serum PTHrP during the course of pregnancy, at term and postpartum have been demonstrated, suggesting that the placenta (during pregnancy) and mammary glands (postpartum) are the main sources of PTHrP. No support for the concept of 'physiological hyperparathyroidism' of pregnancy could be demonstrated in the present work. The ...