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Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering the carbohydrate structures of luteinizing hormone in mice.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2008 May; Vol. 118 (5), pp. 1815-24. - Publication Year :
- 2008
-
Abstract
- Luteinizing hormone (LH), produced in the anterior lobe of the pituitary, is a member of the hypothalamic-pituitary-gonad axis that is required for production of the sex hormones estradiol, progesterone, and testosterone. Perturbations in levels of hormones associated with this axis can result in defects in sexual development and maturity. LH bears unique N-linked carbohydrate units that terminate with a sulfated N-acetylgalactosamine structure (GalNAc-4-SO(4)) that mediates its clearance from the blood. To determine the significance of this terminal structure, we ablated the gene encoding the sulfotransferase responsible for sulfate addition to GalNAc on LH, GalNAc-4-sulfotransferase-1 (GalNAc-4-ST1) in mice. Mice lacking GalNAc-4-ST1 exhibited increased levels of circulating LH. In male mice, this resulted in elevated levels of testosterone and precocious maturation of testis and seminal vesicles. Female mice lacking GalNAc-4-ST1 demonstrated elevated estrogen levels and exhibited precocious sexual maturation and increased fecundity. Female mice remained in estrus for prolonged periods and produced almost 50% more litters per mouse than wild-type mice over the same period of time. Thus, sulfate modification of the terminal glycosylation of LH plays a central role in regulating the hypothalamic-pituitary-gonad axis in vivo.
- Subjects :
- Animals
Estradiol blood
Female
Follicle Stimulating Hormone blood
Luteinizing Hormone blood
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Structure
Organ Size
Seminal Vesicles anatomy & histology
Sulfates chemistry
Sulfates metabolism
Sulfotransferases genetics
Testis cytology
Testis metabolism
Testosterone blood
Uterus anatomy & histology
Carbohydrates chemistry
Luteinizing Hormone chemistry
Reproduction physiology
Sulfotransferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 118
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 18431515
- Full Text :
- https://doi.org/10.1172/JCI32467