Placental lactogen and GH receptors in sheep liver: Striking differences in ontogeny and function
To determine whether changes in the relative biological potencies of ovine placental lactogen (oPL) and ovine growth hormone (oGH) during development derive from ontogenetic changes in the binding of these hormones to hepatic receptors, we have compared the binding of 125I-oPL and 125I-oGH to hepatic membranes from fetal lambs and pregnant sheep at mid- and late gestation and from postnatal sheep at 1 day to 7 mo of age. Specific high-affinity 125I-oPL binding sites in ovine fetal liver were detected as early as day 70 of gestation (term = 145 days), and the number of fetal 125I-oPL binding sites increased progressively throughout the latter half of gestation, reaching a maximum (11.2 fmol/mg protein) at 3-7 days before parturition. The potency of oPL (K(d) 0.27 nM) in competing for 125I-oPL binding sites was 90 and 1,300 times greater than that of oGH and ovine prolactin, respectively. Although the number of fetal 125I-oPL binding sites increased throughout pregnancy, there was little or no specific binding of 125I-oGH noted in the fetus. Treatment of fetal liver membranes with 4 M MgCl2 did not enhance the subsequent specific binding of 125I-oGH, suggesting that the low specific binding of oGH did not result from occupation of hepatic receptors by endogenous circulating oPL or oGH. In contrast, MgCl2 treatment markedly increased the apparent number of fetal 125I-oPL binding sites, suggesting that oPL receptors in fetal liver are partly saturated in vivo by oPL. During the first postpartum week, there were striking increases in the number of 125I-oGH and 125I-oPL binding sites, but the number of 125I-oPL binding sites exceeded the number of 125I-oGH binding sites at all ages. Although the affinity of oGH (K(d), 0.27 nM) for 125I-oGH binding sites in postnatal nonpregnant and pregnant liver was six times higher than the affinity of oGH for postnatal 125I-oPL binding sites, the affinity of oPL for 125I-oPL binding sites in postnatal nonpregnant and pregnant liver (K(d), 0.27 nM) was identical to the affinity of oPL for postnatal 125I-oPL binding sites. These findings suggest the presence of distinct oGH and oPL receptors in pregnant and nonpregnant postnatal sheep liver. Our observations indicate striking differences in the ontogeny of oPL and oGH receptors in sheep liver. oPL receptors, which predominate in fetal liver, appear to mediate the biological effects of oPL in fetal tissues and provide a mechanism whereby oPL may function as a 'growth hormone' in the ovine fetus. On the other hand, oGH receptors appear after birth, facilitating a role for growth hormone in the regulation of ovine growth and metabolism in the postnatal period.
Freemark, M; Comer, M; Handwerger, S
Volume / Issue
International Standard Serial Number (ISSN)