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Open AccessArticle

Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in αT3-1 and LβT2 Gonadotroph Cells

1
Biological & Chemical Sciences, Queen Mary, University of London, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
2
Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, Camden, London NW1 0TU, UK
3
Endocrine Signalling Group, Royal Veterinary College, Royal College Street, Camden, London NW1 0TU, UK
*
Author to whom correspondence should be addressed.
Biology 2019, 8(4), 81; https://doi.org/10.3390/biology8040081
Received: 23 September 2019 / Revised: 18 October 2019 / Accepted: 23 October 2019 / Published: 26 October 2019
(This article belongs to the Section Cell Biology)
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. View Full-Text
Keywords: cortisol; glucocorticoid; pituitary; GnRH; PACAP; gonadotroph; hydroxysteroid dehydrogenase cortisol; glucocorticoid; pituitary; GnRH; PACAP; gonadotroph; hydroxysteroid dehydrogenase
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Michael, A.E.; Thurston, L.M.; Fowkes, R.C. Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in αT3-1 and LβT2 Gonadotroph Cells. Biology 2019, 8, 81.

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