GROWTH HORMONE-BINDING PROTEIN IN HUMAN LYMPH

The high affinity GH-binding protein (GHBP) is a soluble circulating e ctodomain of the GH receptor (GHR). In humans, it is thought to be rel eased from the plasma membrane-bound GHR by proteolysis at or near the transmembrane domain. GHBP modulates GH action by 1) intravascular co mplex formation, and 2) competing with the GHR for ligand in tissues ( interstitial complex formation). Little is known about the tissue sour ce(s) of GHBP, the local regulation of GHBP generation, or its concent ration in the interstitium. To begin addressing these questions, we st udied GHBP levels in peripheral lymph, whose composition approximates that of interstitial fluid. Lymph was collected in 13 healthy adult me n from cannulated lymphatic vessels in the calf. Venous and arterial b lood samples were collected from the femoral vein and radial artery co ntemporaneously with lymph collection. Potential GHBP production by en dothelial or blood cells was assessed by examining conditioned medium from in vitro cell cultures. GHBP activity was measured by standardize d GH binding/column chromatography assay. GHBP was consistently and si gnificantly lower in lymph (mean +/- SD, 4.6 +/- 1.2% GH bound/200 mu L) than in venous (14.1 +/- 3.0%) or arterial (14.9 +/- 3.6%) plasma. Conditioned medium from endothelial or blood cell cultures did not con tain detectable GHBP. We conclude that the level of GHBP in peripheral lymph is substantially lower than that in the peripheral circulation, and that components of the vasculature are not important sources of G HBP. These findings suggests that 1) the main tissue sources of GHBP i n man are the central organs (especially liver); and 2) transcapillary diffusion of GHBP into the interstitial space is restricted.