Australian Regenerative Medicine Institute

Category: Hormone

Hormone-Specific Inhibitory Influence: DISCUSSION(16)

The specific structural changes described in this study, i.e., variations in the length of the Man(al-6)Man branch of Asn56 oligosaccharides, appear to have a greater impact on LH activity than on FSH activity. However, larger oligosaccharides are known to exist on FSH from other species; therefore, those hormones should be investigated inorderto determine how much…

Hormone-Specific Inhibitory Influence: DISCUSSION(15)

It is likely that the nearly 3-fold reduction in intrinsic FSH activity of eLH in the granulosa cell assay as compared with its FSH receptor-binding activity resulted from eLH adopting the same orientation in the FSH receptor as it did in the LH receptor. This had two consequences, increased steric hindrance on the part of…

Hormone-Specific Inhibitory Influence: DISCUSSION(14)

We predicted a functional significance for the a-subunit Asn56 oligosaccharide structural differences between eFSH, eLH, and eCG . However, these oligosaccharide variations were not responsible for different FSH signal-transducing abilities of eLH, eFSH, and eCG. Hybrid preparations composed of eFSH(3 combined with either eLHa or eCGa were predicted to have reduced steroidogenic potencies. Instead, these…

Hormone-Specific Inhibitory Influence: DISCUSSION(13)

Since the effects of Asn56 glycosylation influence the LH receptor-binding activities of eLHp and eCGp hybrids to the same degree as they affect their FSH receptor-binding potencies (unpublished results), it is likely that eLH and eCG adopt the same orientation in the FSH receptor that they maintain when occupying the LH receptor. An alternative hypothesis,…

Hormone-Specific Inhibitory Influence: DISCUSSION(12)

Since a crucial portion of the receptor-binding site in LH and FSH p subunits is different, and possession of both enables binding to both LH and FSH receptors, these hormones may occupy in their receptors with a slightly different orientation. The orientation of LH in its receptor permits engagement of the positively charged determinant loop….

Hormone-Specific Inhibitory Influence: DISCUSSION(11)

Peptide walking experiments identified four regions in hCG as components of its LH receptor-binding site: portions of aL2 and aL3 in the a subunit and PL2 and pL3 in the P subunit. Crystallographic studies on hCG demonstrated that these four regions formed a contiguous surface. Studies on hFSH have implicated three regions in FSH receptor…

Hormone-Specific Inhibitory Influence: DISCUSSION(10)

However, this may occur only in the deglycosylated hormone, as an NMR study by others of the Asn52 oligosaccharide of recombinant hCGa alone and in combination with hCGp indicated no interactions between this oligosaccharide and the peptide moiety of either subunit . The hydrogen bonding observed in the crystal structure of deglycosylated hCG may contribute…

Hormone-Specific Inhibitory Influence: DISCUSSION(9)

Two mechanisms have been proposed to explain how carbohydrate inhibits receptor-binding activity of glycoprotein hormones: 1) blocking of access to the receptor by steric hindrance on the part of the oligosaccharide or 2) alteration in hormone conformation following deglycosy-lation that increases receptor-binding affinity. The latter mechanism is based in part on low-resolution circular di-chroism studies….

Hormone-Specific Inhibitory Influence: DISCUSSION(8)

Increased FSH receptor-binding activity observed with N56dg-a:eFSH(b hybrid preparations as compared with the corresponding intact a:eFSH@ hybrid preparations was modest. This may help to explain the conflicting reports on the influence of haAsn52 oligosaccharide on recombinant hFSH binding to its receptor . As these recombinant hFSH preparations were expressed in three different cell lines, i.e.,…

Hormone-Specific Inhibitory Influence: DISCUSSION(7)

The increase in FSH receptor-binding activity of equine gonadotropin subunit hybrids following PNGase digestion in the analytical-scale experiments was a combination of both increased dimer formation resulting from removal of a steric barrier to dimerization and increased receptor-binding affinity resulting from elimination of a direct inhibitory effect of Asn56 oligosaccharide on receptor binding.

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