title: Gonadotrophin receptor blocking antibodies measured by the use of cell lines stably expressing human gonadotrophin receptors are not detectable in women with 46,XX premature ovarian failure.
abstract: BACKGROUND
  Premature ovarian failure (POF) is defined by cessation of ovarian function after puberty and before the age of 40. The syndrome is characterized by amenorrhoea, oestrogen deficiency and elevated levels of gonadotrophins. Autoimmunity has been proposed as a mechanism for some cases of destruction or malfunction of ovarian follicles. POF is often associated with type I and type II polyglandular autoimmune syndromes. It has also been postulated that receptors such as the LH and FSH receptors might become targets for blocking antibodies and such antibodies could be a cause of ovarian failure.
  
  
  METHODS
  Sixty-nine patients with POF isolated or associated with other endocrine autoimmune diseases (autoimmune thyroid diseases, Addison's disease, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis) were studied. All the patients had secondary amenorrhoea. The patient group had a median age of 33.1 years (range 15-57). Ovarian failure had been diagnosed at a median age of 29 years (range 15-39). The median time since diagnosis was almost 1 year but in six patients gonadal insufficiency had appeared 10-30 years earlier. All had a normal chromosomal karyotype (46, XX). Patients with POF were characterized by duration of amenorrhoea > 1 year, with elevated FSH and LH levels and undetectable or low oestrogen levels. Cell lines stably expressing recombinant human LH (CHO-LHr) and FSH (CHO-FSHr) receptors were prepared and used to search for antibodies able to inhibit LH- or FSH-stimulated cAMP production. Immunoglobulins extracted from sera of patients with POF were incubated with CHO-LHr and CHO-FSHr in the presence of human recombinant CG and FSH, respectively.
  
  
  CONCLUSIONS
  None of the immunoglobulin G (IgG) preparations from patients with POF was able to inhibit the activity of the FSH- and CG-stimulated cAMP production.
authors.affiliation: Dipartimento di Endocrinologia e Metabolismo, Università di Pisa, Pisa, Italy. mtonacchera@hotmail.com
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ferrarini
authors.forename: Antonio
authors.initials: A
authors.lastname: Dimida
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Marco
authors.forename: Melissa
authors.initials: M
authors.lastname: De Servi
authors.forename: Elena
authors.initials: E
authors.lastname: Gianetti
authors.forename: Luca
authors.initials: L
authors.lastname: Chiovato
authors.forename: Enrico
authors.initials: E
authors.lastname: Pucci
authors.forename: Chiara Dal
authors.initials: CD
authors.lastname: Pra
authors.forename: Corrado
authors.initials: C
authors.lastname: Betterle
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Aghini-Lombardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D019138:Antibodies, Blocking / Q000097:blood*; D016466:CHO Cells; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D016649:Primary Ovarian Insufficiency / Q000276:immunology*; D011967:Receptors, Gonadotropin / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D006063:Chorionic Gonadotropin; D011967:Receptors, Gonadotropin; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP