Identification of the region 285-309 of follicle stimulating hormone receptor as a bioneutralizing epitope.
Structure-function relationship studies of the follicle stimulating hormone and its receptor assume importance as this hormone is essential for folliculogenesis and spermatogenesis in females and males, respectively. The interaction between the hormone and the receptor is complex and not well understood. In vitro studies using synthetic peptides from the extracellular domain of the receptor and corresponding antipeptide antibodies have suggested that the 285-309 region is surface-oriented. Antipeptide antibodies to this region also inhibit hormone-receptor interaction in a dose-dependent manner and the mechanism of inhibition appears to be competitive in nature. To test this hypothesis in an animal model, antibodies to peptide 285-309 from rat follicle stimulating hormone receptor (FSHR) were developed and characterized. These antibodies were able to detect FSHR in rat ovaries by immunohistochemistry. Further, these antibodies were administered into adult female rats and their effect on fertility status was monitored. These antibodies were found to neutralize the biological activity of endogenous receptor, which resulted in the induction of infertility in the treated animals. Thus, bioneutralization of FSHR has been achieved by targeting its region 285-309 in an in vivo system.
Ghosalkar
J D
JD
Division of Structural Biology, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Jehangir Merwanji Street, Parel, Mumbai 400012, India.
Dharma
S J
SJ
Nandedkar
T D
TD
Mahale
S D
SD
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007247:Infertility, Female / Q000209:etiology; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D011962:Receptors, FSH / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D000939:Epitopes; D010446:Peptide Fragments; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone