0163-769X/91/1204-0329$03.00/0 Endocrine Reviews Copyright © 1991 by The Endocrine Society

Vol. 12, No. 4 Printed in U.S.A.

CLINICAL COUNTERPOINT: The Physiology of Placental Lactogen in Human Pregnancy* STUART HANDWERGER Division of Endocrinology, Children's Hospital Medical Center and The Perinatal Research Institute, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229

I. II. III. IV. V. VI. VII. VIII. IX. X.

Introduction Species Differences Plasma Concentrations Biological Actions Actions in Mother Actions in Fetus PL Receptor Regulation of Synthesis and Secretion Future Direction of PL Research Summary

istry and biology of the PLs among species (for review, see Ref. 4). These include the number of synthesized and secreted forms of the hormone, the primary amino acid sequences, the cell types that synthesize the hormone and the biological properties of the hormone. There is a single PL in the human (5) that is synthesized by the syncytiotrophoblast cells of the placenta (6). On the other hand, in the mouse and rat there are two distinct PLs synthesized by placental giant cells, one at midgestation and one late in gestation, that differ in biological properties (4). Because of these species differences, extrapolation of experiments of PL function in subprimate animals to human physiology must be done with caution. As indicated below, however, studies of PL physiology in the pregnant sheep may have relevance to human physiology since the patterns of ovine (o) PL secretion in the mother and fetus during pregnancy are similar to those of hPL in human pregnancy, and the biological actions oPL in postnatal sheep tissues are similar to the biological actions of hPL in human tissues (7, 8).

I. Introduction

P

LACENTAL lactogen (PL), a protein hormone synthesized and secreted by the placenta, has striking homologies in its chemical and biological properties to GH and PRL (1, 2) (Table 1). As discussed in the accompanying paper by Saunders and co-workers (3), considerable information is available about the chemistry of human (h) PL and the molecular biology of the hPL/ hGH gene family. Much less is known about the biological actions of hPL during pregnancy, the mechanisms by which hPL exerts its biological actions, and the factors involved in the regulation of the synthesis and secretion of hPL. This review will focus on the role of hPL in the mother and fetus during pregnancy, emphasizing evidence that strongly suggests a role for hPL as a maternal and fetal "growth hormone." Consideration will also be given to recent studies indicating a role for several novel factors in the regulation of the synthesis and release of hPL.

III. Plasma Concentrations hPL is first detected in maternal plasma at about 6 weeks of gestation (6). The concentration then increases linearly until about the 30th week, when peak concentrations of 5000-7000 ng/ml are reached (Fig. 1). The secretion rate of hPL near term is about 1.0 g/day, a rate considerably greater than that of any other protein hormone (9). The plasma concentrations of hPL in the mother correlate positively with placental mass and are greater in multiple than singleton gestations (10, 11). Throughout gestation, plasma concentrations of hPL exceed those of hPRL and hGH (Table 2). Unlike hGH and hPRL, hPL is not glycosylated and does not undergo post-translational modification. However, a small percent of the hPL in plasma circulates as a high molecular weight species bound to macroglobulin (12). Aberrations of hPL secretion have been detected in many pathological conditions of pregnancy associated

II. Species Differences PLs are synthesized by most primate and subprimate species, but there are important differences in the chemAddress requests for reprints to: Dr. Stuart Handwerger, Division of Endocrinology, Children's Hospital Medical Center, Elland and Bethesda Avenues, Cincinnati, Ohio 45229. * Supported by NIH Grant HD-07447.

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HANDWERGER

330 TABLE 1. Some physical properties of hPL, hPRL, and hGH Property

hPL 21,600 4.8 191

Mol wt Isoelectric point Number of amino acid residues Disulfide bonds Number of identical residues (%)

hPRL

hGH

22,500 4.6 198

21,500 4.6 191

2 us. hGH: 85 vs. hPRL: 13

2

3

[Reproduced with permission from S. Handwerger and M. Freemark: Regulation of Ovarian and Testicular Function (edited by V. B. Mahesh, D. S. Dhindsa, E. Anderson, and S. P. Kalra) Plenum Publishing Corp. New York, 1987, p 399 (84).] i

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