PTH-RELATED PROTEIN IS RELEASED INTO THE MOTHERS BLOOD-STREAM DURING LACTATION - EVIDENCE FOR BENEFICIAL-EFFECTS ON MATERNAL CALCIUM-PHOSPHATE METABOLISM

Recent studies have indicated that parathyroid hot-clone-related prote in (PTHrP) may have important actions in lactation, affecting the mamm ary gland, and also calcium metabolism in the newborn and the mother. However, there are as yet no longitudinal studies to support the notio n of an endocrine role of this peptide during nursing. We studied a gr oup of 12 nursing mothers, mean age 32 Sears, after they had been nurs ing for an average of 7 weeks (B) and also 4 months after stopping nur sing (A). It was assumed that changes occurring between A and B corres pond to the effect of lactation. Blood was assayed for prolactin (PRL) , PTHrP (two-site immunoradiometric assay with sheep antibody against PTHrP(1-40), and goat;antibody against PTHrP(60-72), detection limit 0 .3 pmol/l), intact PTH (iPTH), ionized calcium (Ca2+), 25-hydroxyvitam in D-3 (25(OH)D-3) and 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), alk aline phosphatase (alkP), as well as for creatinine (Cr), protein, pho sphorus (P), and total calcium (Ca). Fasting 2-h urine samples were an alyzed for Ca excretion (CaE) and renal phosphate threshold (TmP/GFR). PRL was significantly higher during lactation than after weaning (39 +/- 10 vs. 13 +/- 9 mu g/l;p = 0.018) and so was PTHrP (2.8 +/- 0.35 v s. 0.52 +/- 0.04 pmol/l;p = 0.002), values during lactation being abov e the normal limit (1.3 pmol/l) in all 12 mothers. There was a signifi cant correlation between PRL and PTHrP during lactation (r = 0.8,p = 0 .002). Whole blood Ca2+ did not significantly change from A (1.20 +/- 0.02 mmol/l) to B (1.22 +/- 0.02, mmol/l), whereas total Ca corrected for protein (2.18 +/- 0.02 mmol/l) or uncorrected (2.18 +/- 0.02 mmol/ l) significantly rose during lactation (2.31 +/- 0.02 mmol/l,p = 0.003 and 2.37 +/- 0.03 mmol/l,p = 0.002, respectively). Conversely, iPTH d ecreased during lactation (3.47 +/- 0.38 vs. 2.11 +/- 0.35 pmol/l, A v s. B,p = 0.02). Serum-levels of 25(OH)D-3 and 1,25(OH)(2)D-3 did not s ignificantly change from A to B (23 +/- 2.3 vs. 24 +/- 1.9 ng/ml and 2 9.5 +/- 6.0 vs. 21.9 +/- 1.8 pg/ml, respectively), Both TmP/GFR and P were higher during lactation than after weaning (1.15 +/- 0.03 vs. 0.8 6 +/- 0.05 mmol/l GF;p = 0.003 and 1.25 +/- 0.03 vs. 0.96 +/- 0.05 mmo l/l,p = 0.002, respectively) as was alkP (74.0 +/- 7.1 vs. 52.6 +/- 6. 9 U/I,p = 0.003). CaE did not differ between A and B (0.015 +/- 0.003 vs. 0.017 +/- 0.003 mmol/l GF, A vs. B, NS). We conclude that lactatio n is accompanied by an increase in serum PRL. This is associated with a release of PTHrP into the maternal blood circulation. A rise in tota l plasma Ca ensues, probably in part by increased bone turnover as sug gested by the elevation of alkP. PTH secretion falls, with a subsequen t rise of TmP/GFR and plasma P despite high plasma levels of PTHrP.