Altered peripheral benzodiazepine receptor density in human granulosa-lutein cells in relation to follicular maturity

Since the introduction of treatment by in vitro fertilization/ embryo transfer (IVF-ET) in humans, a harmless approach to identifying the ovum with a greater chance of producing an implantable embryo has been sought worldwide. Our previous studies indicated a high correlation between degree of follicular maturation and benzodiazepine (BZ) receptor density in rats. We hypothesized that if such a correlation existed in humans, the latter might be used to evaluate degree of follicular maturation and, consequently, its corresponding oocyte competence. We used [³H]PK 11195, a ligand selective to peripheral BZ receptors, to determine their density in human granulosa-lutein (G-L) cells. [³H]PK 11195 bound to G-L cells with high affinity in a saturable manner. Scatchard analysis revealed the presence of a single population of receptors. The average equilibrium dissociation constant and maximal number of receptors (B_max) measured in G-L cells were 3.4 ± 0.2 nM and 608 ± 61 fmol/mg protein, respectively. In G-L cells obtained from individual follicles, a significant increase in the specific binding to peripheral BZ receptors was noted in G-L cells of follicles yielding oocytes at an advanced stage of cumulus maturation or oocytes competent for fertilization and subsequent cleavage. When G-L cells were pooled from all the follicles of each individual woman, the average B_max value of [³H]PK 11195 in G-L cells was 900 ± 127 fmol/mg protein in women who conceived, which was 80% higher (P < 0.01) than in women who did not conceive. We suggest that the remarkable increase in peripheral BZ receptor density in the G-L cells of individual follicles yielding fertilizable oocytes and in G-L cells of women who conceived should be considered as a fast and convenient predictor of the chance of pregnancy with human IVF-ET treatment.