The study shows that a synthetic version of growth hormone‑releasing factor (GRF‑1‑29) quickly binds to and is taken into rat pituitary cells, and that this process needs a type of protein modification (fatty‑acid acylation). Blocking this modification with the drug cerulenin stops the hormone from being internalized, but doesn’t affect its breakdown inside the cell.

The GH-releasing factor (GRF) analogue [His1,Nle27]-GRF(1-29) amide was used to study GRF receptor internalization in cultured rat anterior pituitary cells. The half-life of occupied receptors on the surface was approximately 10 min. Uptake of the analogue was followed by lysosomal breakdown, and receptors taken up were replaced to some extent by newly synthesized receptors, as indicated by reduced surface binding in the presence of cycloheximide. 2,3-Epoxy-4-oxo-7,10-dodecadienamide (cerulenin) inhibited internalization without affecting breakdown of the reduced amount of GRF analogue that entered the cells. The effect was half-maximal at 3 micrograms/ml for 1 h. Cerulenin inhibits fatty acid acylation of proteins. One explanation for its effect on GRF receptor internalization is that fatty acid acylation of a protein (possibly the receptor) is necessary for internalization, because cerulenin also inhibited internalization of the transferrin receptor which is known to be acylated. Cerulenin did not affect internalization of the somatostatin receptor present on the same cells, indicating the specificity of the inhibition.