Immunolocalisation of aromatase regulators liver kinase B1, phosphorylated AMP-activated protein kinase and cAMP response element-binding protein-regulated transcription co-activators in the human testis
Seungmin Ham A B , Kristy A. Brown A C , Evan R. Simpson A D and Sarah J. Meachem A E F
+ Author Affiliations
- Author Affiliations
A Hudson Institute of Medical Research, 27–31 Wright Street, Clayton, Vic. 3168, Australia.
B Department of Obstetrics and Gynaecology, Monash University, Wellington Road and Blackburn Road, Clayton, Vic. 3800, Australia.
C Department of Physiology, Monash University, Wellington Road and Blackburn Road, Clayton, Vic. 3800, Australia.
D Department of Biochemistry and Molecular Biology, Monash University, Wellington Road and Blackburn Road, Clayton, Vic. 3800, Australia.
E Department of Anatomy and Developmental Biology, Monash University, Wellington Road and Blackburn Road, Clayton, Vic. 3800, Australia.
F Corresponding author. Email: sarah.meachem@princehenrys.org
Reproduction, Fertility and Development 29(5) 1029-1038 https://doi.org/10.1071/RD15390
Submitted: 2 October 2015 Accepted: 4 February 2016 Published: 7 March 2016
Abstract
Although oestrogens are essential for spermatogenesis and their biosynthesis is dependent on aromatase expression, the molecular mechanism of aromatase regulation is poorly understood. Our laboratory has demonstrated that liver kinase B1 (LKB1) is a negative regulator of aromatase in the breast by phosphorylating AMP-activated protein kinase (AMPK) and inhibiting the nuclear translocation of the cAMP response element-binding protein-regulated transcription co-activator (CRTC) 2. The aim of this study was to determine the location of testis-associated proteins in the LKB1–CRTC pathway. Aromatase, LKB1, phosphorylated AMPK (pAMPK) and CRTC1–3 were examined by selected immunofluorescent antibodies in testis samples from a prepubertal boy and three fertile men. Aromatase, pAMPK and LKB1 proteins were present in the seminiferous epithelium and interstitium of the testis and were expressed in a differential and developmental manner in particular cell types. The expression pattern of LKB1 was similar to that of pAMPK and inversely related to aromatase expression. CRTC1 and CRTC3 were localised in the seminiferous epithelium, whereas CRTC2 was barely detectable in testis. These results lead to the conclusion that LKB1 is involved in the molecular pathway that underpins aromatase regulation in the testis via CRTC1 and CRTC3 and may be important for the oestrogen-mediated development of germ cells.
Additional keywords: aromatase, spermatogenesis, steroidogenesis.
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