Two free isoforms of ovine glycoprotein hormone α-subunit strongly differ in their ability to stimulate prolactin release from foetal pituitaries

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Abstract

α-Subunit dissociated from glycoprotein hormones has been previously shown to stimulate rat pituitary lactotroph differentiation and proliferation. However, whether the free form of the α-subunit (free α) can also play such a role is not known. To test whether free α may act on prolactin (PRL) release from ovine foetal pituitaries, this molecule was purified and two major isoforms, αA and αB were isolated. Free αA was found to be more acidic and more hydrophobic than both free αB and ovine LH α-subunit (oLHα). Free αA and oLHα exhibited a molecular mass of 14 kDa as determined by mass spectrometry, whereas free αB displayed a molecular mass of only 13.5 kDa because of its truncated N-terminus. All three α molecules bear mature-type N-linked saccharide chains including N-acetyl galactosamine residues but none of them contains O-linked oligosaccharide. The free αA isoform, more than the oLHα, was able to stimulate PRL release from ovine foetal pituitary explants in culture, whereas the free αB isoform displayed no activity. Moreover, the free αA and αB isoforms were able to recombine with the ovine LH β-subunit (oLHβ). The free αB/oLHβ, and the oLHα/oLHβ dimer were 4-fold more active than the free αA/oLHβ dimer in a specific LH radioreceptor assay and in the stimulation of testosterone release from rat Leydig cells. The present study demonstrates that the two free α isoforms of ovine glycoprotein hormones exhibit distinct efficiencies in stimulating PRL release from ovine foetal pituitaries. Moreover, despite their identical ability to recombine with the oLHβ, the free α isoform, which is the most efficient on PRL release, is the least efficient in conferring LH activity on the α/β dimer.

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Chabot, V., Magallon, T., Taragnat, C., & Combarnous, Y. (2000). Two free isoforms of ovine glycoprotein hormone α-subunit strongly differ in their ability to stimulate prolactin release from foetal pituitaries. Journal of Endocrinology, 164(3), 287–297. https://doi.org/10.1677/joe.0.1640287

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