Reactivity of Non-Primate Growth Hormones and Prolactins with Human Growth Hormone Receptors on Cultured Human Lymphocytes

Abstract

Ovine placental lactogen is as reactive as human growth hormone with the human growth hormone receptor of cultured human (IM-9) lymphocytes, which confirms the findings of Carr and Friesen with receptors of human liver. We now also show that bovine and ovine growth hormones and ovine prolactin have reactivity for the human growth hormone receptor on IM-9 lymphocytes that is of the same order of magnitude (0.03%) as that previously reported for human placental lactogen. The binding studies predict that these non-primate hormones will have biological effects on skeletal growth in primates, either as agonists or antagonists. Previous studies have shown that when IM-9 lymphocytes are exposed to human growth hormone for 18 h at 37 C, there is a time and concentration dependent loss of human growth hormone receptors, and the magnitude of the loss of receptors after preincubation for 18 h at 37 C is greater than the average occupancy of receptors under steady state conditions for 90 min at 30 C. In the present study we show that human and ovine placental lactogens, ovine prolactin, and bovine and ovine growth hormones also produce this effect on the human growth hormone receptor. Since the cellular process by which a hormone induces loss of its own receptors appears to require binding of the hormone to its receptor as well as one or more subsequent steps in hormone action, it is likely that all of the preparations that induce receptor loss will be shown to have some agonist activity of human growth hormone in promoting skeletal growth in primates. Further, these studies extend the interrelationships between primate and non-primate pituitary and placental hormones from what has been suggested previously from biological and structural studies.