title: Low levels of follicle-stimulating hormone receptor-activation inhibitors in serum and follicular fluid from normal controls and anovulatory patients with or without polycystic ovary syndrome.
abstract: In patients with normogonadotropic anovulation, either with or without polycystic ovary syndrome (PCOS), factors interfering with FSH action may be involved in arrested follicle development. The aim of this study is to assess whether factors inhibiting FSH receptor activation are elevated in serum or follicular fluid from anovulatory patients, as compared with regularly cycling women. For this purpose, a Chinese hamster ovary cell line, stably transfected with the human FSH receptor, has been applied. FSH-stimulated cAMP secretion in culture medium was measured in the presence of serum or follicular fluid. Chinese hamster ovary cells were stimulated with a fixed concentration of FSH (3 or 6 mIU/mL) to mimic FSH levels in serum or follicular fluid. Samples were added in concentrations ranging from 3-90% vol/vol to approach protein concentrations occurring in serum or follicular fluid. In the presence of 10% vol/vol serum from regularly cycling women (n = 8), FSH-stimulated cAMP production was inhibited to 42 +/- 2% (mean +/- SEM of 2 experiments, each performed in duplicate) of cAMP production in the absence of serum, whereas a similar cAMP level (up to 38 +/- 4% of the serum-free level) was observed at higher concentrations of serum (30-90% vol/vol). The inhibition of FSH-stimulated cAMP production in the presence of serum samples from normogonadotropic anovulatory patients, without (n = 13) or with (n = 16) PCOS, was similar to controls. Follicular fluid samples (n = 57) obtained during the follicular phase in 25 regularly cycling women and follicular fluid samples (n = 25) from 5 PCOS patients were tested in a slightly modified assay system. In the presence of 10 or 30% (vol/vol) follicular fluid, FSH-stimulated cAMP levels were decreased to 68 +/- 2% and 55 +/- 2% (mean +/- SEM of a single experiment in triplicate) of the cAMP levels in the absence of follicular fluid, respectively. There was no correlation between the degree of cAMP inhibition and follicle size, steroid content (androstenedione or estradiol concentrations), or menstrual cycle phase. Furthermore, no differences in inhibition were found, comparing PCOS follicles with size- and steroid content-matched follicles obtained during the normal follicular phase. It is concluded that inhibition of FSH receptor activation by proteins present in serum or follicular fluid is constant (60 and 40%, respectively) and independent from the developmental stage of the follicle, either during the normal follicular phase or in patients with normogonadotropic anovulation. Inhibition of FSH receptor activation may be of limited significance for normal and arrested follicle development.
authors.affiliation: Department of Obstetrics and Gynecology, Dijkzigt Academic Hospital and Erasmus University Medical School, Rotterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Schipper
authors.forename: F F
authors.initials: FF
authors.lastname: Rommerts
authors.forename: P M
authors.initials: PM
authors.lastname: Ten Hacken
authors.forename: B C
authors.initials: BC
authors.lastname: Fauser
mesh_terms: D000328:Adult; D000818:Animals; D000858:Anovulation / Q000097:blood* / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D015571:Follicular Fluid / Q000378:metabolism*; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000378:metabolism*; D011962:Receptors, FSH / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics; D014162:Transfection
chemical_list: D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP