Effects of carbohydrates on the pharmacokinetics and biological activity of equine chorionic gonadotropin in vivo.

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.

Genetic and temporal variation in serum concentrations and biological activity of horse chorionic gonadotrophin.

The variation in the quantity of circulating chorionic gonadotrophin (CG) and its follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity in rodent bioassay systems was investigated. A portion of the variability in total CG could be attributed to the stallion that sired the pregnancy and it was possible to select sires and mares to increase CG production. It was further demonstrated that FSH activity per unit of CG was greater at Days 71 and 104 of gestation than at Day 39. LH activity per unit of CG varied with the sire, but no effect of day of gestation could be shown. It was demonstrated that removal of sialic acid increased LH bioactivity and it is proposed that variation in biological activity between animals and during gestation may be a function of differences in carbohydrate content of CG.