Abstract
Purpose:
We hypothesize that the growth hormone (GH) / insulin-like growth factor 1 (IGF-1) axis plays a significant role in the regulation of the meibomian gland. In support of this hypothesis, we have discovered that IGF-1 activates the PI3K/AKT and inhibits forkhead box O1 signaling pathways, stimulates cellular proliferation, increases the expression of sterol regulatory element-binding protein, promotes lipid accumulation, and inhibits the isotretinoin-induced late apoptosis/necrosis in human meibomian gland epithelial cells. To continue to test our hypothesis, we examined the influence of GH on mouse meibomian gland structure.
Methods:
We utilized several mouse strains, including: [a] bovine (b) GH transgenic mice with excess GH and IGF-1 action; [b] GH antagonist (A) transgenic mice with decreased GH and IGF-1 action; [c] GH receptor (R) knockout (-/-) mice with no GH activity, and corresponding low levels of IGF-1; and [d] wild type (WT) control mice. Adult mice were sacrificed, and eyelids removed and processed for sectioning and H&E staining. Glandular sizes were quantified with ImageJ.
Results:
Our results show that the morphology of WT and bGH meibomian glands appear normal. In contrast, there are striking structural changes in the GH-deficient animals. Many of the GHR-/- and GHA meibomian glands featured hyperkeratinized and thickened ducts, acini inserting into duct walls, and poorly differentiated acini. In addition, preliminary analyses suggest that leukocytes may accumulate in the GH-deficient glands. Grossly, meibomian glands of bGH mice were significantly larger, and those of GHA and GHR-/- mice significantly smaller, than glands of WT mice.
Conclusions:
Our findings support our hypothesis that the GH/IGF-1 axis plays a significant role in the control of the meibomian gland. In addition, our data show that GH modulates the size and morphology of this tissue.