Differential regulation of inhibin B rand inhibin A by follicle-stimulating hormone and local growth factors in human granulosa cells from small antral follicles

Serum inhibin B rises across the luteal-follicular transition, whereas inhi bin A does not increase until the late follicular phase of the menstrual cy cle. To test the hypothesis that inhibin B is secreted from preantral and s mall antral follicles and that FSH and local growth factors differentially regulate inhibin B and inhibin A from these developing follicles, human ova ries were obtained after oophorectomy. Basal secretion of inhibin B and inh ibin A was examined in intact preantral follicles in culture (n = 6). Basal secretion and regulation of inhibin B and inhibin A secretion by gonadotro pins, androstenedione, activin A, insulin, and IGF-I were examined in cultu red granulosa cells from small antral follicles (n = 21). Inhibin B secreti on from preantral follicle cultures was detectable at baseline (range, 17-9 6 pg/mL), whereas inhibin A was not detectable. In contrast, both inhibin B and inhibin A were detectable in granulosa cell cultures from small antral follicles. In granulosa cells from small antral follicles, FSH (30 ng/mL) stimulated inhibin A 3-fold (10.5 +/- 2.2 to 32.5 +/- 8.3 IU/mL; P < 0.001) , but not inhibin B secretion (1730 +/- 354 to 2314 +/- 532 pg/mL; P = NS). Likewise, cAMP (1 mmol/L) stimulated inhibin A 4-fold (16.6 +/- 4.3 to 62. 5 +/- 21.9 IU/mL; P < 0.002), but not inhibin B secretion (2327 +/- 546 to 1877 +/- 377 pg/mL; P = NS). hCG (30 ng/mL) did not stimulate inhibin A or inhibin B. Androstenedione (10-7 mol/L), activin (30 ng/mL), insulin (30 ng /mL), and insulin-like growth factor I (IGF-I; 100 ng/mL) alone did not sti mulate inhibin A or inhibin B secretion. Further, FSH-stimulated inhibin A secretion was not augmented by androstenedione, activin, insulin, or IGF-I. In contrast, the combination of IGF-I and FSH was the only treatment that stimulated inhibin B secretion (1742 +/- 380 to 2881 +/- 731 pg/mL; P < 0.0 3). However, FSH in combination with IGF-T resulted in greater stimulation of inhibin A (340%) than inhibin B (65%). These findings demonstrate that inhibin B is secreted from developing prean tral and small antral follicles, but is not directly stimulated by FSH. How ever, the combination of FSH and IGF-I enhanced inhibin B secretion. In con trast, inhibin A is not secreted from preantral follicles, but in small ant ral follicles FSH and cAMP stimulate inhibin A secretion. Further, FSH in c ombination with IGF-I results in a greater degree of stimulation of inhibin A than of inhibin B. These findings suggest that FSH and IGF-I differentia lly regulate inhibin A and inhibin B secretion. However, additional growth factors or increasing granulosa cell number may contribute to the preferent ial serum inhibin B increase across the luteal-follicular transition in the menstrual cycle.