Researchers found that a protein called RECK, which sits on cell membranes in the pituitary gland, is important for making growth hormone (GH) and keeping the GH/IGF‑1 system working properly in mice. When RECK levels are lowered, mice get smaller, have less IGF‑1 in their blood, and show reduced GH production and fewer GH‑related receptors, even though the genes for those receptors are more active.

The tumor suppressor gene Reversion-inducing cysteine-rich protein with Kazal motifs (Reck) encodes a membrane-anchored protease regulator expressed in multiple tissues in mouse embryos and is essential for embryonic development. In postnatal mice, however, physiological roles for the RECK protein remain unclear. We found in this study that Reck is abundantly expressed in growth hormone (GH)-producing cells (somatotrophs) in the anterior pituitary gland (AP). We also found that two types of viable Reck mutant mice, one with reduced RECK expression (Hypo mice) and the other with induced Reck deficiency from 10 days after birth (iKO mice treated with tamoxifen), exhibit common phenotypes including decreases in body size and plasma levels of insulin-like growth factor-1 (IGF1). To gain insights into the function of RECK in the AP, we characterized several somatotroph-associated molecules in the AP of these mice. Immunoreactivity of GH was greatly reduced in tamoxifen-treated iKO mice; in these mice, two membrane receptors involved in the stimulation of GH secretion [growth hormone secretagogue receptor (GHSR) and growth hormone releasing hormone receptor (GHRHR)] were decreased, however, their mRNAs were increased. Decrease in GHSR immunoreactivity and concomitant increase in its mRNA were also found in the other mutant line, Hypo. Furthermore, reduced immunoreactivity of growth hormone receptor (GHR) and concomitant increase in its mRNA was also found in the liver of Hypo mice. These results raise the possibility that RECK supports proper functioning of the GH/IGF1 axis in mice, thereby affecting their growth and metabolism.