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
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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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Female mice heterozygous for deletion of the Man/GalNAc-4-SO4 receptor o...
Female mice heterozygous for deletion of the Man/GalNAc-4-SO4 receptor ovulate normally but have a reduced rate of implantation. (a) Eggs were collected from genotyped mice the morning following estrus and counted. An unpaired t test indicated that the mean values of 8.2 for M/G4S-R+/– female mice and 8.7 for M/G4S-R+/+ female mice were not significant (P = 0.40). (b) Genotyped mice were given subcutaneous injections of P4 (2 mg per mouse) on day 3, and P4 (2 mg per mouse) + E2 (10 ng per mouse) on day 4. Mice were injected with Chicago sky blue 6B in saline on day 5 shortly before sacrifice, and the number of implantation sites demarcated as localized blue bands (8) was counted. Bars indicate the median. ANOVA analysis using Tukey’s multiple comparison test indicated that the difference between the mean value of 5.1 for M/G4S-R+/– female mice and 8.6 for M/G4S-R+/+ female mice is significant (P < 0.05) whereas the difference between the means of 7.1 for M/G4S-R+/– female mice treated with P4 and E2 and 8.6 for M/G4S-R+/+ female mice was not significant (P > 0.05).