Sex Hormones, Growth Hormone, and the Cornea

Abstract

The growth and maintenance of nearly every tissue in the body is influenced by systemic hormones during embryonic development through puberty and into adulthood. Of the ~130 different hormones expressed in the human body, steroid hormones and peptide hormones are highly abundant in circulation and are known to regulate anabolic processes and wound healing in a tissue-dependent manner. Of interest, differential levels of sex hormones have been associated with ocular pathologies, including dry eye disease and keratoconus. In this review, we discuss key studies that have revealed a role for androgens and estrogens in the cornea with focus on ocular surface homeostasis, wound healing, and stromal thickness. We also review studies of human growth hormone and insulin growth factor-1 in influencing ocular growth and epithelial regeneration. While it is unclear if endogenous hormones contribute to differential corneal wound healing in common animal models, the abundance of evidence suggests that systemic hormone levels, as a function of age, should be considered as an experimental variable in studies of corneal health and disease.

Keywords: cornea; estradiol; estrogen; growth hormone; insulin growth factor-1; wound healing.

Figure 1

Biosynthesis of androgens and estrogens from cholesterol. Cholesterol is converted to pregnenolone and then 17-hydroxypregnenolone before synthesis of dehydroepiandrosterone (DHEA). The common precursor, androstenedione, can be converted to the primary estrogens or testosterone in a tissue-dependent manner. The adrenal cortex is the primary site of C19-hormone synthesis from cholesterol in humans. Estrone may also be converted to estradiol via the enzyme 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1) (not shown). (Abbreviations: 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2), 17β-hydroxysteroid dehydrogenase type 3 or 5 (17βHSD3/5), cytochrome P450 aromatase (P450aro), and cytochrome P450 3A4 (CYP3A4)).

Figure 2

Comparative study of male and female rabbit corneas following wounding. Hematoxylin and eosin stain of unwounded and wounded (A,C) male and (B,D) female rabbit corneas. Image re-produced from [49] with permission (https://doi.org/10.1016/j.exer.2019.107705, accessed 13 December 2021).

Figure 3

Relative changes in stromal thickness as a function of the menstrual cycle. Data based on the average central corneal thickness (CCT) reported at each stage in references [57,58,59]. Mean ± standard error shown, with n = 3.

Figure 4

Activation of the GH/IGF-1 axis promotes pro-survival mechanisms. GH secreted from the pituitary gland may promote an increase (↑) in systemic IGF-1, a ligand of the IGF1R receptor, leading to activation of the ERK1/2 and MAPK kinases and downstream activators.