ABSTRACT
The abnormal functionality of the mutant FSH receptors in vitro provides a rational explanation for their implication in the development of spontaneous OHSS in vivo. During pregnancy, the expression of FSH receptors decreases dras tically in the corpus luteum, but remains con stant in granulosa cells of developing follicles19. These receptors are usually not or very weakly stimulated during pregnancy, as pituitary gonadotropins fall to very low or undetectable levels in the serum. In the presence of a mutation rendering them abnormally sensitive to hCG, these receptors are stimulated under the action of pregnancy-derived hCG, resulting in the recruitment and growth of a follicular
Figure 2 Functional characteristics of the four follicle stimulating hormone (FSH) mutant receptors identified in patients presenting spontaneous OHSS. Levels of cyclic adenosine monophosphate (cAMP) observed using COS-7 cells transfected with wild-type human FSH receptor (wt hFSHr), D567N, D567G mutants (a) and T449I, T449A mutants (b) after stimulation with recombinant human (rh) FSH (lOIU/ml) and increasing concentrations of recombinant human chorionic gonadotropin (rhCG) (100-300 IU/ml). Each graph represents the mean ± SEM of at least two separate experiments
cohort. Accordingly, the follicles enlarge and acquire LH receptors on granulosa cells which are further stimulated by hCG, inducing follicu lar luteinization together with the secretion of vasoactive molecules responsible for develop ment of the syndrome.
