An examination of the proposed roles of placental lactogen in the ewe by means of antibody neutralization

Abstract

The physiological role of placental lactogen (PL; chorionic somatomammotrophin) in the ewe has been investigated by infusion of ewes (n = 3) on day 131 of pregnancy with sufficient ovine PL (oPL) antibody to neutralize circulating oPL for at least 12 h. Effectiveness of the antibody neutralization was defined both in vitro and in vivo according to rigorous criteria. Control ewes (n = 3) were infused simultaneously with an equivalent amount of pooled goat gamma globulin. Since both sets of ewes had previously been catheterized with jugular, utero-ovarian and femoral vein catheters and a femoral arterial catheter, it was possible to measure whole body glucose kinetics as well as muscle and uterine glucose, free fatty acid (FFA) and 3-hydroxybutyrate extraction. In addition, plasma levels of insulin, GH, prolactin, insulin-like growth factor-I (IGF-I), IGF-II, progesterone and cholesterol were determined in femoral arterial samples. Neutralization of maternal oPL did not significantly affect whole body glucose metabolism, uterine and muscle glucose extraction, or 3-hydroxybutyrate extraction by muscle. A trend towards lower plasma FFA levels was observed after prolonged infusion, but was not statistically significant. However, plasma insulin levels rose significantly during antibody infusion after an early fall. These observations are rationalized in terms of the known requirements of ruminant metabolism during pregnancy, and contrasted with the accepted model for the role of human PL in the metabolic adjustments of pregnancy. No change in plasma IGF-I, IGF-II or GH was observed, providing no support for the concept that oPL is responsible for maternal somatomedin generation during pregnancy. Similarly, plasma prolactin did not differ between antibody-treated and control groups. Finally, antibody neutralization had no influence on either plasma progesterone or cholesterol, mitigating against a role for oPL in progesterone production during late pregnancy in the ewe.

Untitled

“…Interestingly, more recently it has been suggested that PL and placental GH act in concert to modulate maternal metabolism, resulting in an increase in the available supply of glucose and amino acids to the fetus [9]. Studies concerning the effect sheep PL may have on pancreatic function however, are not definitive [40-42]. The short-term removal of oPL by immunoneutralisation increased insulin concentration [42], while an acute oPL infusion failed to demonstrate any significant changes in insulin levels [41].…”

Hormones of the Placenta: hCG and hPL

“…In the sheep, maternal hyperglycaemia produces no change in PL levels in fetus or ewe (Brinsmead et al, 1981). Also in the sheep, neutralization of PL by antibodies does not affect glucose metabolism, or the circulating levels of somatomedins, growth hormone, progesterone or cholesterol (Waters et al, 1985).…”

“…Similarly, infusion of corticosteroids or corticotrophin has no effect on circulating oPL levels (Taylor et aI., 1983a); agents such as chlorpromazine and thyrotropin-releasing hormone, which produce a significant increase in fetal prolactin levels, have no effect on fetal oPL (Tay-lor et al, 1983b). Neutralization of oPL by in vivo administration of antibody to oPL appears to have no effect on glucose, fatty acids, somatomedins or growth hormone, but causes a fall followed by a rise in insulin levels (Waters et al, 1985). In vitro, phospholipase C can stimulate oPL release (Rice and Thorburn, 1986).…”

Failure of fasting and changes in plasma metabolites to affect spontaneous fluctuations in plasma concentrations of ovine placental lactogen

“…In fed pregnant ewes, oPL levels were moderately increased during 4 days of intensive study, but plasma FFA concentrations remained unchanged. When oPL concentrations were transiently lowered by immunoneutralization, plasma FFA levels were unchanged (Waters et al 1985). Finally, while mean plasma oPL concentrations increase continuously during the last two thirds of gestation (Handwerger et al 1977;Butler, Fullenkamp, Capiello & Handwerger, 1981), marked fluctuations during periods of frequent sampling suggest that secretion of oPL is quite dynamic.…”

“…In such a model, increased avail¬ ability of FFA for maternal metabolism would be facilitated by oPL depression of insulin secretion(Falconer, Owens, Allotta & Robinson, 1985;Waters, Oddy, McCloghry et al 1985). When tested directly, however, acute oPL administration resulted in a decline in plasma FFA levels, rather than an increase…”