Control of follicle-stimulating hormone by estradiol and the inhibins: critical role of estradiol at the hypothalamus during the luteal-follicular transition.
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 alpha-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 alpha-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.
Welt
Corrine K
CK
Reproductive Endocrine Unit and National Center for Infertility Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. cwelt@partners.org
Pagan
Yanira L
YL
Smith
Patricia C
PC
Rado
Kimberly B
KB
Hall
Janet E
JE
D004958:Estradiol / Q000502:physiology*; D025461:Feedback, Physiological; D005640:Follicle Stimulating Hormone / Q000097:blood* / Q000378:metabolism; D005498:Follicular Phase; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000172:deficiency; D007031:Hypothalamus / Q000502:physiology*; D007265:Inhibins / Q000097:blood / Q000502:physiology*; D008183:Luteal Phase; D007986:Luteinizing Hormone / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D013629:Tamoxifen / Q000494:pharmacology
D011960:Receptors, Estrogen; C422362:inhibin A; C422364:inhibin B; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone