Intracellular signaling by growth hormone variant (GH-V)☆
Section snippets
INTRODUCTION
The human GH gene cluster contains five structural genes:1 hGH (pituitary GH gene), expressed by somatotropes in the anterior pituitary, hCS-A and hCS-B, the two chorionic somatomammotropin genes expressed in the placenta (also known as human placental lactogen, hPL), and hCS-L, chorionic somatomammotropin-like gene. In addition, Seeburg reported the existence of a growth hormone-variant gene or GH-V, in 1982.2 Subsequent gene expression was localized to the villous syncytiotrophoblasts.[3], [4]
Reagents
Recombinant human growth hormone (rhGH) and recombinant human prolactin (rhPrl) were from Genentech (San Francisco, CA). The hCS was purchased from Sigma (St. Louis, MO). The enhanced chemiluminescence kit (ECL) was purchased from Amersham (Arlington Heights, IL). Anti-phosphotyrosine antibody was a monoclonal (py99) from Santa Cruz Biotechnology (Santa Cruz, CA). Polyclonal STAT5a and STAT5b specific antibodies were developed in our laboratory.20 Peptides used to generate the antibodies
RESULTS
Using cell model systems which are known targets of pituitary growth hormone (rhGH or GH-N) action,[24], [25], [26] we have investigated the ability of placental growth hormone or growth hormone-variant (GH-V) to activate similar signaling. Importantly, we have also tested the effect of human chorionic somatomammotropin (hCS, or human placental lactogen/hPL) in these model systems in order to determine which effects are specific to GH-V. These studies are aimed at not only understanding the
DISCUSSION
We have shown that human placental growth hormone variant (GH-V) activates the signal transducer and activator of transcription, STAT5b, in a manner similar to that seen with human pituitary growth hormone (GH-N). GH-N and GH-V both activate STAT5b in GH receptor-expressing cell models, while the related placental hormone, human chorionic somatomammotropin (hCS), does not. However, in the Nb2 cell model which expresses Prl receptors, but not GH receptors, GH-N, GH-V, hCS, and Prl all activate
Acknowledgements
We thank Dr. Nancy Cooke and Dr. Stephen Liebhaber for the C127 cells, Dr. Arthur Buckley for the Nb2 cells, and Dr. Gary Owens for the smooth muscle cells. In addition, we thank Dr. Christian Strasburger and Dr. Zida Wu for their measurements of recombinant GH-V. We are especially grateful for helpful conversations and critical reading of the manuscript by Dr. Eugene Barrett.
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Supported in part by NIH Grants R29-DK48481 and 3M01-RR00847-22S1.