GROWTH HORMONE IN HUMAN PREGNANCY: Maternal 24-hour Serum Profiles and Experimental Effects of Continuous GH...

Growth hormone (GH) concentrations in serum were recorded in healthy women at different stages of normal pregnancy. Using a non-thrombogenic venous catheter and a portable pump, blood samples were collected at 30 min intervals for a period of 24 h. Growth hormone serum profiles were also established in non-pregnant women, women undergoing legal abortion and cesarean section and during spontaneous labor. A dramatic change in growth hormone secretion was demonstrated during late pregnancy when compared with the non-pregnant state. The pulsatile pattern, with intermittent high peaks and low or undetectable levels between peaks, characteristic of normal men and non-pregnant women, was completely suppressed. During late pregnancy, all investigated women evidenced increased, very stable serum levels of GH and there was no evidence of pulsatile activity. Two monoclonal antibodies directed against different epitopes on the GH-molecule were used in radio-immunoassays to distinguish the pituitary 22K-GH from other circulating GH variants. During the second half of pregnancy, a continuous secretion of a new placental GH variant and a concommitant suppression of the pulsatile pituitary GH secretion was demonstrated. The progressive transformation of GH secretion from a pulsatile into a stable, continuous pattern started at the end of the first trimester. After placental removal at cesarean section in late pregnancy there was a rapid fall in serum GH concentration, whereas levels were unaffected after legal abortion in the first trimester. These results and simultaneous measurements of hPL and hCG support the concept that a placental GH variant is produced during pregnancy. Studies on the diurnal variations of thyrotropin, prolactin and cortisol indicate that human pregnancy is associated with selective alterations in the secretion of pituitary hormones. The biological impact of continuous GH secretion was elucidated in two experimental systems in the rat. The pregnancy-associated murine protein-1 (PAMP-1) in rodents was previously believed to be regulated by sex steroids. However, a continuous infusion of hGH was found to increase the plasma concentration of PAMP-1 in non-pregnant, hypophysectomized female rats. On the other hand, intermittent hGH administration or estrogen treatment had no effect on this seemingly 'steroid-sensitive' protein. Steroid sulfatase activity in rat liver microsomes is another sexually differentiated function. Likewise, this system was found to be regulated by the mode of GH administration. A continuous GH secretion during human pregnancy can alter maternal liver metabolism and have important implications for the physiological adjustment to gestation.