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

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

Authors

A E Michael

L M Thurston

R C Fowkes



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, 11β-hydroxysteroid dehydrogenase (11βHSD; 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 αT3-1, LβT2 (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 αT3-1 and LβT2 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 11βHSD enzyme(s). Stimulation of both gonadotroph cell lines with either 100 nM GnRH or PACAP (known physiological regulators of gonadotrophs) resulted in significantly increased 11β-dehydrogenase (11βDH) and 11-ketosteroid reductase (11KSR) activities, over both 4 and 24 h. These data reveal that gonadotroph 11βHSD 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 Oct 29, 2019
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

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