Endocrine Abstracts

The gonadotrophin receptors, LH receptor (LHR) and FSHR are G-protein coupled receptors, vital in mediating reproductive functions. During the follicular phase of the ovarian cycle, FSHR and LHR are separately localised to discrete cellular compartments, granulosa and theca cells respectively, where they control steroidogenesis and follicle maturation. However, as the follicle develops, LHR expression is induced in granulosa cells, resulting in co-expression of FSHR and LHR in a single cellular compartment. Remarkably, little is known about the functional significance of this co-expression. While both FSHR and LHR are known to homodimerise, the question of whether FSHR and LHR can form functional heterodimers remains to be explored. Therefore, this study aims to determine if FSHR and LHR can form heterodimers and assess the functional impact of such heterodimer formation. The ability of FSHR and LHR to heterodimerise in live, intact cells was observed through the use of bioluminescence resonance energy transfer. The ability of the heterodimer to impact receptor cell surface expression showed no significant effects on cell surface trafficking of either receptor. Further, Gαs/cAMP signalling was not altered in the LHR/FSHR heterodimer compared to cells expressing each receptor alone. Interestingly, the pattern of LHR-induced Gαq/calcium signalling was significantly altered in the presence of FSHR, from an acute and rapid signal to a more sustained calcium response. The prolonged calcium signal from LH activated LHR/FSHR expressing cells appears to be mediated through activation of L-type calcium channels. Use of a Gαi inhibitor, pertussis toxin, had no effect on calcium signalling indicating there may be no alteration in G protein-coupling of the heterodimer. The mechanisms underlying this change in calcium signalling patterns will be further assessed. Overall this study indicates that LHR/FSHR heterodimers may represent a key mechanism for generating sustained calcium responses in preovulatory follicles.

Declaration of funding

BBSRC grant number BB/1008004/1.