Low-glycosylated forms of both FSH and LH play major roles in the natural ovarian stimulation

Abstract

Background: The natural ovarian stimulation is mediated by four gonadotrophin glycoforms: FSHtri with three, FSHtetra with four, LHdi with two, and LHtri with three N-glycans. The aim of the study was to determine the serum concentrations of the four glycoforms and their contents of anionic monosaccharides (AMS), i.e. sialic acid (SA) and sulfonated N-acetylgalactosamine (SU) residues throughout the menstrual cycle.

Methods: Serum samples were collected from 78 healthy women with regular menstrual cycles. The serum glycoform molecules were identified by their distributions at electrophoreses. Analyses were also performed after removal of terminal SA. The hormones were measured with time-resolved sandwich fluoroimmunoassays.

Results: The concentration profiles of the four glycoforms were markedly different. FSHtri, which had a 3-fold higher biopotency than FSHtetra, had peak levels on cycle day 5 and at midcycle and nadirs on cycle days 9 and 21–23. FSHtetra had a raised level on cycle days 5–12, followed by a decrease. LHdi and LHtri had similar patterns, but the peak/nadir ratio was much more pronounced for LHdi than for LHtri, 18 versus 4. The numbers of SA residues per molecule were at a maximum around midcycle when the corresponding numbers of SU were at a minimum. The SU/SA ratio was at a minimum on cycle day 12.

Conclusion: The results indicate that the LHdi and the FSHtri molecules play major roles in the natural ovarian stimulation. The SU/SA ratios per molecule favoured a prolonged circulatory half-life of all glycoforms at the midcycle phase. The observations may lead to more successful inductions of ovulation in anovulatory women.

Keywords:

• FSH glycoforms
• LH glycoforms
• normal menstrual cycle
• ovulation induction
• sulfonated N-acetylgalactosamine
• sialic acid

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by grants from Uppsala University.

Notes on contributors

Leif Wide

Leif Wide, M.D., PhD, Professor Emeritus of Endocrinological Biochemistry, Uppsala University, Uppsala, Sweden.

Karin Eriksson

Karin Eriksson, B.Sc. Graduate engineer, Uppsala University, Uppsala, Sweden.