Effects of carbohydrates on the pharmacokinetics and biological activity of equine chorionic gonadotropin in vivo.
Abstract: The sialylation of eCG was examined to determine its influence on the in vivo metabolism and biological activity of the molecule. Sialic acid was decrementally removed from eCG by incubation with agarose-linked neuraminidase for varying time periods. Pharmacokinetic parameters for the disappearance of 4,000 IU (267 micrograms) of three desialylated eCG preparations (20%, 53%, and 80% sialic acid removed) and control eCG were determined in sheep. The clearance rate of eCG increased (p less than 0.05) with each decrement of sialic acid. The removal of 53% sialic acid enhanced the distribution of eCG into the tissues, compared to control and 20% desialylated eCG (p less than 0.05), presumably because of increased lipid solubility and decreased molecular size. Desialylation to 53% did not alter the elimination half-life of eCG. The removal of 80% sialic acid resulted in the disappearance of eCG from the serum within 1 h, whereas control eCG was still present at 120 h. In vivo trials in rats disclosed that the control eCG preparation increased ovulatory rate at doses of 10-100 IU and ovarian weight at doses of 10-300 IU relative to saline-treated rats (p less than 0.01). The 20% desialylated eCG induced superovulatory and ovarian weight responses, but 100-500 IU were required to achieve the same result as that produced by control eCG. The 53% and 80% desialylated eCG preparations induced a mild superovulatory response (p less than 0.01) but no ovarian weight response. It was concluded that sialic acid was significant to the distribution and disappearance of eCG. The effects of carbohydrate removal on biological activity (e.g., superovulation) are primarily a function of clearance rate rather than tissue-specific phenomena.
Publication Date: 1991-10-01 PubMed ID: 1751634DOI: 10.1095/biolreprod45.4.598Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research explores how the alteration of the carbohydrate content of equine chorionic gonadotropin (eCG), a hormone, impacts its function and absorption in the body. The study finds that changes in carbohydrate composition can affect the distribution, clearance rate and overall effectiveness of eCG, with implications for medical and veterinary applications.
Methodology and Procedures
- The researchers investigated the effect of reducing sialic acid (a type of carbohydrate) content in eCG by incubating it with agarose-linked neuraminidase for varying periods.
- Pharmacokinetic parameters were determined for three desialylated eCG preparations (20%, 53%, and 80% sialic acid removed) and the unmodified control eCG by injecting these into sheep and monitoring disappearance rate.
- In vivo trials on rats were conducted to evaluate the impact of control and desialylated eCG preparations on ovulation rate and ovarian weight.
Key Findings and Conclusions
- The clearance rate of eCG was found to increase with each reduction of sialic acid content. This suggests that the absorption and elimination of eCG in the body is partially dependent on the level of sialic acid.
- A 53% reduction of sialic acid increased the distribution of eCG into the tissues, presumably because of increased lipid solubility and decreased molecular size.
- The removal of 80% sialic acid resulted in eCG quickly disappearing from the serum, suggesting a rapid clearance from the body.
- In vivo trials showed that the unmodified control eCG effectively increased ovulatory rate and ovarian weight in rats, with the same effects requiring a larger dose for the 20% desialylated eCG. The 53% and 80% desialylated eCG versions had minimal to no impact on ovulation and ovarian weight.
- The reduction of sialic acid in eCG was concluded to have significant implications on its distribution, absorption, and overall biological function, with the effects primarily a product of clearance rate rather than tissue-specific phenomena.
Cite This Article
APA
Martinuk SD, Manning AW, Black WD, Murphy BD.
(1991).
Effects of carbohydrates on the pharmacokinetics and biological activity of equine chorionic gonadotropin in vivo.
Biol Reprod, 45(4), 598-604.
https://doi.org/10.1095/biolreprod45.4.598 Publication
Researcher Affiliations
- Department of Obstetrics and Gynecology, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
MeSH Terms
- Animals
- Biological Assay
- Chorionic Gonadotropin / blood
- Chorionic Gonadotropin / pharmacokinetics
- Female
- Gonadotropins, Equine / blood
- Gonadotropins, Equine / pharmacokinetics
- N-Acetylneuraminic Acid
- Neuraminidase
- Rats
- Rats, Inbred Strains
- Sheep
- Sialic Acids / pharmacology
- Superovulation
Citations
This article has been cited 9 times.- Likszo P, Gromadzka-Hliwa K, Klos J, Kaczmarek MM, Ziecik AJ. Attainment of Sexual Maturity and Gonadotropin Priming in Gilts Determine Follicular Development, Endocrine Milieu and Response to Ovulatory Triggers. Int J Mol Sci 2022 Aug 16;23(16).
- Luna-Palomera C, Macías-Cruz U, Sánchez-Dávila F. Superovulatory response and embryo quality in Katahdin ewes treated with FSH or FSH plus eCG during non-breeding season. Trop Anim Health Prod 2019 Jun;51(5):1283-1288.
- Alvarez RH, Natal FL, Ribela MT, de Almeida BE, de Oliveira JE, Bartolini P. Physical-chemical and biological characterization of different preparations of equine chorionic gonadotropin. J Vet Sci 2016 Dec 30;17(4):459-465.
- Cohen L, Bousfield GR, Ben-Menahem D. The recombinant equine LHβ subunit combines divergent intracellular traits of human LHβ and CGβ subunits. Theriogenology 2015 Jun;83(9):1469-76.
- Arming S, Wipfler D, Mayr J, Merling A, Vilas U, Schauer R, Schwartz-Albiez R, Vlasak R. The human Cas1 protein: a sialic acid-specific O-acetyltransferase?. Glycobiology 2011 May;21(5):553-64.
- Klett D, Bernard S, Lecompte F, Leroux H, Magallon T, Locatelli A, Lepape A, Combarnous Y. Fast renal trapping of porcine luteinizing hormone (pLH) shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life. Reprod Biol Endocrinol 2003 Oct 6;1:64.
- Bottino JP, Ungerfeld R, Taira AR, Santos JDR, Beltramo M, Brandão FZ. The Kisspeptin analogue C6 induces more synchronized ovulation than eCG in the transition period to breeding season in Corriedale ewes. Trop Anim Health Prod 2025 Dec 12;57(9):541.
- Lösle M, Lin CW, Beil-Wagner J, Aebi M, Buch T. Comparison of pregnant mare serum gonadotropin products with surprising differences in protein content. Sci Rep 2025 Feb 25;15(1):6824.
- Thompson RE, Meyers MA, Palmer J, Veeramachaneni DNR, Magee C, de Mestre AM, Antczak DF, Hollinshead FK. Production of Mare Chorionic Girdle Organoids That Secrete Equine Chorionic Gonadotropin. Int J Mol Sci 2023 May 31;24(11).
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