Abstract
ContextThe progestins of the levonorgestrel family are 13-ethylgonane progestins, commonly used for contraception in women. One contraceptive effect of these progestins is inhibition of ovulation, which may be a result of changes in gonadotropin glycosylation patterns. Gonadotropin glycoforms differ in number of glycans and bioactivity: more bioactive low-N-glycosylated glycoforms, diglycosylated luteinizing hormone (LHdi) and triglycosylated follicle-stimulating hormone (FSHtri), and less bioactive fully N-glycosylated glycoforms, LHtri and FSHtetra.ObjectiveCharacterize the glycosylation patterns on the circulating gonadotropin glycoforms in women using 13-ethylgonane progestins for contraception.Design, Subjects, Main Outcome MeasuresSerum samples, collected from 92 healthy women using 13-ethylgonane progestins for contraception, were included. Forty women used progestin-only continuously and 52 used progestins combined with ethinylestradiol (EE) for 3 weeks followed by a hormone-free week. Concentration, sulfonation, and sialylation of each glycoform were determined and compared with follicular phase values of normal menstrual cycles.ResultsThe progestin-only group had significantly increased serum levels, decreased sulfonation, and increased sialylation of LHdi. The LHdi/FSHtri ratio was increased. The progestin+EE group had significantly decreased gonadotropin glycoform concentrations and decreased sialylation of FSHtri. The progestin+EE effect on sialylation of FSHtri occurred later during the treatment cycle in contrast to the effect on FSHtri concentration.ConclusionsThe 2 different progestin treatments induced different effects on the glycan synthesis and concentrations of more bioactive low-glycosylated gonadotropins. Progestin-only treatment increased sialylation and decreased sulfonation of LHdi molecules, contributing to sustained higher levels of bioactive LHdi molecules. Progestin+EE treatment decreased sialylation of FSHtri, contributing to a shorter half-life and decreased levels of bioactive FSHtri.
Highlights
Context: The progestins of the levonorgestrel family are 13-ethylgonane progestins, commonly used for contraception in women
The LHdi concentration and the ratio of low-glycosylated glycoforms (LHdi/FSHtri) were significantly higher in the progestin-only group compared with the follicular phase group
We report in this study that the glycosylation pattern on gonadotropin glycoform molecules in serum samples of women using, for contraception, progestin-only or progestin+EE is different from that during the follicular phase of normal menstrual cycles
Summary
Context: The progestins of the levonorgestrel family are 13-ethylgonane progestins, commonly used for contraception in women. Gonadotropin glycoforms differ in number of glycans and bioactivity: more bioactive low-N-glycosylated glycoforms, diglycosylated luteinizing hormone (LHdi) and triglycosylated follicle-stimulating hormone (FSHtri), and less bioactive fully N-glycosylated glycoforms, LHtri and FSHtetra. Objective: Characterize the glycosylation patterns on the circulating gonadotropin glycoforms in women using 13-ethylgonane progestins for contraception. The term gonane is used for the basic 17-carbon steroid nucleus, the cyclopentanoperhydrophenanthrene, and the term progestin for a synthetic progestogen [3, 4] These 13-ethylgonane progestins are commonly in use for contraception in women. We have found that all 3 pituitary glycoprotein hormones, FSH, luteinizing hormone (LH), and thyrotropin (thyroidstimulating hormone; TSH) circulate in blood as low-Nglycosylated and fully N-glycosylated forms differing in total number of glycans: FSHtri and FSHtetra; LHdi and LHtri; and TSHdi and TSHtri, respectively [10]. The low-N-glycosylated forms of FSH, LH, and TSH are less sialylated and such molecules exhibit a higher bioactivity at the target cells compared with the more sialylated fully N-glycosylated forms [13,14,15,16,17,18,19,20,21,22,23,24]
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