Regulation of lutropin circulatory half-life by the mannose/N-acetylgalactosamine-4-SO4 receptor is critical for implantation in vivo
Yiling Mi, … , Steven D. Shapiro, Jacques U. Baenziger
Yiling Mi, … , Steven D. Shapiro, Jacques U. Baenziger
Published January 15, 2002
Citation Information: J Clin Invest. 2002;109(2):269-276. https://doi.org/10.1172/JCI13997.
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Article

Regulation of lutropin circulatory half-life by the mannose/N-acetylgalactosamine-4-SO4 receptor is critical for implantation in vivo

Abstract

Lutropin (LH) directs ovulation and implantation by regulating the production of estrogen and progesterone. We have shown that the circulatory half-life of LH is controlled by the Man/GalNAc-4-SO4 receptor, which binds GalNAc-4-SO4 on LH oligosaccharides. The short half-life in conjunction with episodic release of LH from the pituitary accounts for the pulsatile rise and fall in circulating LH. Complete genetic ablation of the Man/GalNAc-4-SO4 receptor results in death in utero. Heterozygous female mice clear LH from the circulation more slowly and have smaller litters due to a reduction in the rate of implantation. This reduction is fully correctable by exogenous progesterone and estrogen, indicating that the rate of LH clearance is critical for the production of sufficient progesterone and estrogen for implantation. Thus, the Man/GalNAc-4-SO4 receptor regulates the endocrinological status of the female and is essential for an early event in embryonic development.

Authors

Yiling Mi, Steven D. Shapiro, Jacques U. Baenziger

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Generation of Man/GalNAc-4-SO4 receptor+/– mice. (a) The Man/GalNAc-4-SO...
Generation of Man/GalNAc-4-SO4 receptor+/– mice. (a) The Man/GalNAc-4-SO4 receptor targeting construct. The 5′ and 3′ homologies were derived from exon 2, which encodes the entire cysteine-rich domain of the receptor, and its flanking introns. Exon 2 was replaced with a PGK-neo cassette. (b) DNA from the live progeny of heterozygous matings was genotyped by PCR or Southern blotting. The wild-type locus was detected using primers P1 and P2, which yielded a 421-bp product, and the mutant locus using primers P3 and P4, which yielded a 548-bp product. No Man/GalNAc-4-SO4 receptor–/– animals lived to birth. Examples of PCR reactions from M/G4S-R+/+ and M/G4S-R+/– mice are shown. Std, oligonucleotide standard.