Effects of long-acting recombinant human follicle-stimulating hormone analogs containing N-linked glycosylation on murine folliculogenesis.
OBJECTIVE
To evaluate the efficacy of two novel long-acting rhFSH analogs, rhFSH-N2 and rhFSH-N4, in stimulating murine folliculogenesis.


METHODS
Experimental study.


METHODS
Academic research environment.


METHODS
Immature female mice.


METHODS
Recombinant hFSH-N2 and -N4 were administered via single IP injection to 3-week-old female mice (n = 10) who were killed 48 hours later for dissection and histologic examination of reproductive organs and serum inhibin A. Results were compared with other groups of mice who received either single or q 12 hour injections for 48 hours of commercial rhFSH, or a single injection of pregnant mare serum gonadotropin (PMSG). A subgroup of the mice receiving rhFSH-N4 was supplemented with daily injections of small doses of hCG to simulate LH add-back.


METHODS
Serum inhibin A levels, ovarian and uterine weights, and ovarian antral follicle counts.


RESULTS
Recombinant human FSH-N2 and -N4 administration induced a statistically significant increase in ovarian weights, uterine weights, and inhibin A levels compared with single and twice-daily injection of rhFSH. PMSG induced the greatest increases in all three measured parameters. There was no statistical difference between rhFSH-N2 and rhFSH-N4 for any parameter analyzed. A single injection of rhFSH-N2 or -N4 induced a greater number of antral follicles than did either single or q 12 hour injections of rhFSH. The addition of small doses of hCG to rhFSH-N4 increased inhibin A levels and antral follicle number to reach statistical equivalence to PMSG treatment.


CONCLUSIONS
Addition of a synthetic polypeptide containing two or four N-linked glycosylation sites to rhFSH increases in vivo bioactivity of the hormone compared to commercial rhFSH. After a single injection, both rhFSH-N2 and rhFSH-N4 effectively induced a greater follicular response in the mouse than did rhFSH.
Ruman
Jane I
JI
Long Island Fertility and Endocrinology IVF Associates, Lake Success, New York, NY, USA.
Pollak
Susan
S
Trousdale
Rhonda K
RK
Klein
Jeffrey
J
Lustbader
Joyce W
JW
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology*; D006031:Glycosylation; D006064:Gonadotropins, Equine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism / Q000494:pharmacology*; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods*; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology
D043373:Follicle Stimulating Hormone, Human; D006064:Gonadotropins, Equine; D009844:Oligosaccharides; D011994:Recombinant Proteins