Endocrine Abstracts

The human Short-chain alcohol Dehydrogenase Reductase (SDR) superfamily of oxoreductase enzymes regulate important endocrine hormones. Two SDR members, 11b-hydroxysteroid dehydrogenase (11bHSD) 1 & 2 have key roles in the pre-nuclear receptor modification of glucocorticoid steroids, thereby contributing to regulation of fluid homeostasis, blood pressure, metabolic pathways and brain function. We have recently characterised a third structurally related HSD enzyme, 11B-HSD1L or HSD3, which is specially restricted, with an absence in the majority of rodent genomes. 11bHSD1L/HSD3 displayed highest expression in the brain, pituitary and gonads (1). Immunohistochemistry analysis in the sheep, marmoset and macaque showed strong protein localisation to the granulosa cells of the ovary and to the gonadotrophs of the anterior pituitary. Further studies now show that the 11bHSD1L gene in primates but not the sheep undergoes alternate splicing at the 3’end to generate mRNAs with different exon 9-derived sequences to produce two isoforms, 11bHSD1L9A and 11bHSD1L9B. Both splice variants are expressed in the pituitary but only the 9A form in the ovary. We have further localised expression of 11bHSD1L9B to the gastrointestinal tract (GIT) and immunofluorescent imaging in the marmoset showed strong protein localisation to enteric endocrine cells in the small and large intestine. Finally, an antibody directed to the 11bHSD1L9B isoform detected localisation of 11bHSD1L9B to pituitary lactotrophs. Overall, these results suggest that 11bHSD1L may play regulatory roles in reproduction through actions in the pituitary-gonadal axis and in also in the GIT.

Reference

1. Bird AD, Greatorex S, Reser D, Lavery GG, Cole TJ (2017) Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary–gonadal axis of primates. Endocrine Connections 6: 489–499.