High density lipoproteins stimulate placental lactogen release and adenosine 3',5'-monophosphate (cAMP) production in human trophoblast cells: evidence for cAMP as a second messenger in human placental lactogen release.

Abstract:

:Recent studies from our laboratory indicate that high density lipoproteins (HDL) and apolipoproteins-AI, -AII, and -CI stimulate the release of human placental lactogen (hPL) from human placental explants and trophoblast cells. However, the intracellular mechanisms by which HDL stimulate hPL release are unknown. Since earlier investigations from our laboratory indicated that pharmacological agents that increase intracellular cAMP levels [such as (Bu)2cAMP, isobutylmethylxanthine, and cholera toxin] also stimulate hPL release, we have performed studies to determine whether the stimulation of hPL release by HDL may be mediated by cAMP. Exposure of an enriched fraction of enzymatically dispersed hPL-producing cells to HDL (10-1500 micrograms/ml) for 0.5 h resulted in a significant dose-dependent stimulation of both cAMP production and hPL release. The half-maximal effective HDL dose for cAMP production and hPL release was 60-100 micrograms/ml. When perifused trophoblast cells were exposed to HDL (150 micrograms/ml) for 25 min, the increase in cAMP production preceded the increase in hPL release. The increase in cAMP production occurred during the first 5 min of exposure to HDL and reached a maximum (12.1 +/- 1.6-fold greater than base-line levels) 10 min after exposure. The increase in hPL release occurred about 10 min after the initial increase in cAMP production, reaching a maximum (9.7 +/- 1.4-fold greater than base-line levels) 15 min after exposure to HDL. HDL (300 micrograms/ml) also stimulated a 2.7-fold (P less than 0.001) increase in adenylate cyclase activity in placental plasma membranes, a magnitude of stimulation comparable to that caused by epinephrine (1 mM). Apolipoprotein-AII stimulated cAMP formation and hPL release in trophoblast cells with a pattern identical to that of HDL. These results, the first to demonstrate an effect of HDL on adenylate cyclase activity and cAMP production, strongly suggest a role for cAMP as a second messenger in HDL-stimulated hPL release.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Wu YQ,Jorgensen EV,Handwerger S

doi

10.1210/endo-123-4-1879

subject

Has Abstract

pub_date

1988-10-01 00:00:00

pages

1879-84

issue

4

eissn

0013-7227

issn

1945-7170

journal_volume

123

pub_type

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