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Control of Follicle-Stimulating Hormone by Estradiol and the Inhibins: Critical Role of Estradiol at the Hypothalamus during the Luteal-Follicular Transition

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

Address all correspondence and requests for reprints to: Corrine K. Welt, Reproductive Endocrine Unit, BHX 511, Fruit Street, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: cwelt{at}partners.org.

To test the hypothesis that estradiol, inhibin A, and inhibin B contribute differentially to FSH negative feedback in specific phases of the menstrual cycle, daily blood samples were obtained across a control cycle and after selective estrogen blockade with tamoxifen. To examine the site of estradiol-negative feedback in control and tamoxifen treatment cycles, early follicular phase GnRH (free -subunit) pulse frequency was assessed in normal women, and FSH levels were examined in GnRH-deficient women in whom hypothalamic output was fixed with GnRH administration. FSH was higher in the early follicular phase in the presence of estrogen receptor blockade (15.7 ± 3.1 vs. 13.2 ± 1.9 IU/liter; P < 0.05) but was not increased in the late follicular phase. In the luteal phase, FSH was elevated (10.1 ± 0.7 vs. 7.3 ± 0.6 IU/liter; P < 0.01). In normal women, free -subunit pulse frequency increased (7.3 ± 0.4 vs. 4.8 ± 0.4 pulses per 8 h; P < 0.003), but in GnRH-deficient women, there was no FSH increase (11.1 ± 1.6 vs. 12.5 ± 3.6 IU/liter) in the early follicular phase in the presence of estrogen blockade. In conclusion, estradiol exerts a greater role over inhibin in FSH-negative feedback regulation during the luteal phase and the luteal-follicular transition. In contrast, inhibin A and/or B plays a more critical role as the follicular phase progresses. In addition, these studies support a primary if not exclusive hypothalamic site of estrogen-negative feedback in the early follicular phase.

This work was supported by NIH Grants U54-HD-29164, M01-RR-01066, and K24-HD-01290.

Abbreviation: FAS, Free -subunit.

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