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Differential Regulation of Inhibin A and Inhibin B by Luteinizing Hormone, Follicle-Stimulating Hormone, and Stage of Follicle Development¹

Reproductive Endocrine Unit, Reproductive Endocrine Sciences Center, and National Center for Infertility Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Dr. Corrine K. Welt, Reproductive Endocrine Unit, BHX 511, Fruit Street, Massachusetts General Hospital, Boston, Massachusetts 02114.

Abstract

Inhibin B and inhibin A exhibit unique patterns of secretion across the follicular phase of the menstrual cycle. To test the hypothesis that the distinct patterns of inhibin B and inhibin A secretion result from differential regulation by LH and FSH, a series of controlled experiments was designed to dissect the specific effects of LH and FSH at distinct stages of follicle development. After GnRH agonist desensitization, women with small antral follicles were treated with recombinant human LH (rhLH), rhFSH, or rhFSH and estradiol (E₂). rhLH or rhFSH was also administered when follicles reached the preovulatory stage in gonadotropin-stimulated or spontaneous cycles.

At the small antral stage of development, rhFSH, but not rhLH, administration increased inhibin B (17.4 ± 4.6 to 321.0 ± 97.0 pg/mL; P < 0.05), inhibin A (0.6 ± 0.1 to 2.6 ± 0.6 IU/mL; P < 0.05), and E₂ [15.8 ± 3.6 to 95.3 ± 26.9 pg/mL (58.0 ± 13.2 to 349.8 ± 98.7 pmol/L); P < 0.05]. The inhibin B increase preceded inhibin A by 48 h. Addition of E₂ to FSH resulted in a greater increase in inhibin B (23.2 ± 6.4 to 865.2 ± 294.5 pg/mL; P < 0.05) than FSH alone (P < 0.05). At the preovulatory stage, rhLH administration increased inhibin A (15.9 ± 10.3 to 21.5 ± 13.7 IU/mL; P < 0.05) and E₂ [669.4 ± 285.5 to 943.6 ± 388.1 pg/mL (2457.4 ± 1048.1 to 3464.0 ± 1424.7 pmol/L); P < 0.05], but not inhibin B, as did rhFSH administration in spontaneous cycles [E₂: 226.4 ± 102.7 to 264.7 ± 121.0 pg/mL (831.1 ± 377.0 to 971.7 ± 444.2 pmol/L); P < 0.05; inhibin A: 2.6 ± 1.3 to 3.7 ± 1.9 IU/mL; P < 0.05; and inhibin B: 76.3 ± 32.2 to 77.6 ± 32.8 pg/mL; P = NS].

These findings suggest that increases in both FSH and E₂ in the early follicular phase result in increased inhibin B secretion at early stages of follicle development, whereas the selective LH rise in the late follicular phase favors inhibin A secretion from more mature follicles. Thus, both differential secretion of LH and FSH and the stage of follicle development determine the patterns of inhibin A and inhibin B secretion in the normal menstrual cycle.

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