The sera of 26 patients with premature ovarian failure were examined in order to detect immunoglobulin-G (IgGs) that can block FSH-induced in vitro granulosa cell DNA synthesis via, a Feulgen cytochemical bioassay system. The IgGs of four patients with polycystic ovary-like disease, five postmenopausal women, and four eumenorrheic women served as controls. Ovarian growth blocking IgGs were found in 21 of the 26 premature ovarian failure (POF) cases. The few cases characterized by the absence of follicles (streak ovaries) and the controls were negative. The ovarian blocking IgGs were far more prevalent in the POF cases than anti-cytoplasmic ovarian antibodies detected by an indirect immunofluorescence assay (only one of the 26 POF patients was positive). Our data hence confirm earlier expressed views that immune mechanisms are involved in a high proportion of patients with POF.
Pituitary FSH as well as urinary FSH were found to be potent stimulators of in vitro granulosa cell DNA synthesis in Wistar rat ovarian segments kept in organ culture. Optimal responses were reached at the highest concentration used (pituitary FSH, 5 mU/mL: urinary FSH, 50 mU/mL). hCG also appeared to be a potent stimulator (optimal response, 5 mU/mL). LH showed no stimulating effect, but the hormone had a potentiating effect on FSH-induced DNA synthesis. Plasma samples of five normally menstruating women obtained at different stages of the follicular phase were also added to the rat ovarian culture system. All samples stimulated DNA synthesis, but the plasma samples obtained in the late follicular phase showed stronger growth responses, reaching optimal values at lower concentrations compared to the potency of plasma obtained in the early follicular phase (10(-3)-10(-5) vs. 10(-2)-10(-3) mL, respectively). The strong bioeffect of late follicular phase plasma could partly be explained by the potentiating effects of plasma LH on FSH-induced DNA synthesis. When plasma samples of five hypergonadotropic amenorrheic women were added to the culture system, 4 stimulated DNA synthesis moderately, with an optimal growth response at plasma concentrations of 10(-4)-10(-3) mL. When 10 plasma samples of hypogonadotropic amenorrheic women were added to the culture system, 8 had no effect on DNA synthesis, and clear discrepancies were evident between the low to absent ovarian growth potential of the plasma and the practically normal immunoreactive plasma FSH measured by RIA and immunoradiometric assay. These discrepancies may be the effect of nonimmune or immune factors interfering with FSH-induced growth or the effect of molecular changes in the FSH molecule (isoforms).
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