Leydig Cells During Blockade of the Androgen Receptor

Michael Scally MD

Doctor of Medicine
10+ Year Member
Highlights
· Androcur prevented testosterone-reduced Leydig cells steroidogenic capacity/activity
· Androcur completely abolished testosterone-reduced expression of Tspo,StAR,Hsd3b1/2
· Androcur abolished testosterone-reduced expression of Nur77,Gata4,Dax1 transcripts
· Androcur abolished testosterone-induced increase of Hsd3b5/HSD3B and Ar/AR
· Androcur abolished testosterone-reduced cAMP and milieu of cAMP signaling elements

Bjelic MM, Stojkov NJ, Baburski AZ, et al. Molecular adaptations of testosterone-producing leydig cells during systemic in vivo blockade of the androgen receptor. Molecular and Cellular Endocrinology. https://www.sciencedirect.com/science/article/pii/S030372071400241X

This study systematically evaluates the effects of androgen receptor (AR) blockade on molecular events in Leydig cells. Results showed that intramuscular administration of Testosterone-enanthate, at clinically relevant dose, decreased testosterone in interstitial fluid and Leydig cells from adult rats.

AR-blocker (Androcur) prevented this effect and testosterone-reduced Leydig cells steroidogenic capacity/activity.

Testosterone-reduced expression of some steroidogenic enzymes/proteins (Tspo,StAR,Hsd3b1/2) and transcription factors (Nur77,Gata4,Dax1) was completely abrogated, while decreased expression of Star,Cyp11a1,Cyp17a1,Hsd17b4,Creb1a was partially prevented. In the same cells, increased expression of Hsd3b5/HSD3B and Ar/AR was abolished.

Androcur-treatment abolished testosterone-reduced cAMP, coupled with a changed expressional milieu of cAMP signaling elements.

Results from in vitro experiments suggest that some of these effects are testosterone-AR dependent, while others could be due to disturbed LH and/or other signals.

Presented data provide new molecular insight into Leydig cells function and are important in terms of human reproductive health and the wide-spread use of Androcur as well as use/abuse of Testosterone-enanthate.
 
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