Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in aT3-1 and LßT2 Gonadotroph Cells

Michael, A E; Thurston, L M; Fowkes, R C

Abstract

The regulation of reproductive function by glucocorticoids occurs at all levels of the hypothalamo-pituitary-gonadal axis. Within the pituitary, glucocorticoids have been shown to directly alter gene expression in gonadotrophs, indicating that these cell types are sensitive to regulation by the glucocorticoid receptor. Whilst the major glucocorticoid metabolising enzymes, 11?-hydroxysteroid dehydrogenase (11?HSD; HSD11B1 and HSD11B2), have been described in human pituitary adenomas, the activity of these enzymes within different pituitary cell types has not been reported. Radiometric conversion assays were performed in ?T3-1, L?T2 (gonadotrophs), AtT-20 (corticotrophs) and GH3 (somatolactotrophs) anterior pituitary cell lines, using tritiated cortisol, corticosterone, cortisone or 11-dehydrocorticosterone as substrates. The net oxidation of cortisol/corticosterone and net reduction of cortisone/11-dehydrocorticosterone were significantly higher in the two gonadotroph cells lines compared with the AtT-20 and GH3 cells after 4 h. Whilst these enzyme activities remained the same in ?T3-1 and L?T2 cells over a 24 h period, there was a significant increase in glucocorticoid metabolism in both AtT-20 and GH3 cells over this same period, suggesting cell-type specific activity of the 11?HSD enzyme(s). Stimulation of both gonadotroph cell lines with either 100 nM GnRH or PACAP (known physiological regulators of gonadotrophs) resulted in significantly increased 11?-dehydrogenase (11?DH) and 11-ketosteroid reductase (11KSR) activities, over both 4 and 24 h. These data reveal that gonadotroph 11?HSD enzyme activity can act to regulate local glucocorticoid availability to mediate the influence of the HPA axis on gonadotroph function.

Citation

Michael, A. E., Thurston, L. M., & Fowkes, R. C. (2019). Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in aT3-1 and LßT2 Gonadotroph Cells. Biology, 8(4), 81. https://doi.org/10.3390/biology8040081

• Journal Article Type: Article
• Acceptance Date: Oct 23, 2019
• Publication Date: Oct 26, 2019
• Deposit Date: Oct 29, 2019
• Publicly Available Date: Nov 20, 2020
• Journal: Biology
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 4
• Pages: 81
• DOI: https://doi.org/10.3390/biology8040081
• Public URL: https://rvc-repository.worktribe.com/output/1379969