Abstract
Vol.39 No.1
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Original
Development of a recombinant murine luteinizing hormone-binding protein as a selective hormone inhibitor
JMOR, 39(1) 35-47, 2022
Physiological levels of gonadotropins promote follicular development and ovulation. However, high luteinizing hormone (LH) levels associated with diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) can inhibit these processes. Here, we developed a mouse LH-binding protein (mLBP) as a selective inhibitor of mouse LH to ultimately permit in vivo analysis of the association between a high LH environment and follicular development disorders in mice with DOR or POI. mLBP was produced as a soluble protein by incorporating the extracellular-encoding domain of mouse LH receptor genes into an expression system for membrane-immobilized fusion proteins. The binding affinity of mLBP for mouse LH was confirmed using sera containing high levels of LH and follicle stimulating hormone (FSH) collected from ovariectomized (OVX) mice. The activity of mLBP was demonstrated by inhibition of cAMP and testosterone production induced by OVX-mouse serum in mouse Leydig-derived MLTC-1 cells expressing LH receptors. In contrast, mLBP neither bound mouse FSH nor inhibited cAMP production induced by OVX mouse serum in 293 cells expressing mouse FSH receptors. mLBP also exhibited binding affinity for human LH (hLH) and inhibited hLH-induced cAMP production in MLTC-1 cells. Thus, mLBP was demonstrated to selectively suppress the actions of mouse and human LH.
