Hypo-glycosylated hFSH binds and activates FSH receptors more rapidly than fully-glycosylated hFSH
Bousfield, George R.
Butnev, Vladimir Y.
May, Jeffrey V.
Harvey, David J.
Davis, John S.
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George Russell Bousfield, Vladimir Y Butnev, Jeffrey V May, David J Harvey, Chao Jiang, and John S Davis Hypo-glycosylated hFSH binds and activates FSH receptors more rapidly than fully-glycosylated hFSH. FASEB J. April 2013 27 (Meeting Abstract Supplement) 592.2
Follitropin (FSH) heterodimers possess two potential N-glycosylation sites on both common α and hormone-specific β subunits. Hypo-glycosylated hFSH isolated from lutropin preparations possessed a partially glycosylated FSHβ subunit decorated with one glycan, while there were two in the hFSHα subunit. Mass spectrometry revealed the presence of oligomannose glycans, which are normally rare in hFSH preparations. Hypo-glycosylated hFSH was 5- to 26-fold more active than fully-glycosylated hFSH in several FSH radioligand assays. In rat testis homogenate, 125I-hypo-hFSH bound receptors immediately, without the 45–60 min lag observed for 125I-fully-glycosylated hFSH. In porcine granulosa cells, short-term incubations revealed an earlier onset of cAMP accumulation, protein kinase A (PKA) activity and CREB phosphorylation. Hypo-glycosylated hFSH increased intracellular cAMP accumulation within one min and PKA-dependent CREB phosphorylation within 5 min; whereas fully-glycosylated hFSH induced CREB phosphorylation after a 10–15 min lag. Additionally, CREB phosphorylation was sustained for greater than 60 min in response to hypo-glycosylated hFSH, but returned to basal within 60 min in response to fully-glycosylated hFSH. Thus, partial glycosylation of hFSH results in faster binding to its cognate receptor and this is attended by a more rapid cellular response.
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Presented at the Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) Boston, MA, APR 20-24, 2013.
- BIO Faculty Publications