Generating FSH antagonists and agonists through immunization against FSH receptor N-terminal decapeptides.
J Mol Endocrinol
; 22(2): 151-9, 1999 Apr.
Article
en En
| MEDLINE
| ID: mdl-10194518
Follicle-stimulating hormone (FSH) via interaction with G-protein coupled specific receptors plays a central role in the control of gametogenesis in mammals of both sexes. In females, FSH is crucial for follicle growth, follicle maturation and ovulation. FSH receptors, together with luteinizing hormone-chorionic gonadotropin and thyrotropin receptors belong to a subfamily of structurally related receptors within the seven transmembrane receptor family. Among several other regions, the N-terminus of these receptors is believed to be responsible for important specific hormone-receptor contact sites. Recombinant filamentous phages displaying at their surface three overlapping N-terminal decapeptides of the FSH receptor, peptides A18-27, B25-34 and C29-38 were constructed. Ewes and female mice were immunized against the three FSH receptor (FSHR) recombinant phages. Immunoglobulins purified from immunized animals were analyzed for their biochemical properties on a Chinese hamster ovary cell line expressing the porcine FSH receptor. AntiA and antiB immunoglobulins (IgGs) behave as antagonists for 125I-FSH binding and for FSH-dependent cAMP production, while antiC IgGs did not compete for hormone binding. By contrast, antibodies against the C29-38 peptide displayed FSH agonist activity and stimulated the FSH receptor, whereas antiA and antiB IgGs did not. Furthermore, when the FSHR phages were used as peptidic vaccines, they induced a reversible inhibition of ovulation rate in ewes, and impaired fertility in female mice.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de HFE
/
Hormona Folículo Estimulante
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
J Mol Endocrinol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Año:
1999
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido