This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Welt, C. K. Articles by Hall, J. E. Search for Related Content PubMed PubMed Citation Articles by Welt, C. K. Articles by Hall, J. E.

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.

This article has been cited by other articles:

				D. M. Robertson, G. E. Hale, D. Jolley, I. S. Fraser, C. L. Hughes, and H. G. Burger Interrelationships between Ovarian and Pituitary Hormones in Ovulatory Menstrual Cycles across Reproductive Age J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 138 - 144. [Abstract] [Full Text] [PDF]

				Y. Wang, J. Fortin, P. Lamba, M. Bonomi, L. Persani, M. S. Roberson, and D. J. Bernard Activator Protein-1 and Smad Proteins Synergistically Regulate Human Follicle-Stimulating Hormone {beta}-Promoter Activity Endocrinology, November 1, 2008; 149(11): 5577 - 5591. [Abstract] [Full Text] [PDF]

				W. E. Ottowitz, D. D. Dougherty, A. J. Fischman, and J. E. Hall [18F]2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Demonstration of Estrogen Negative and Positive Feedback on Luteinizing Hormone Secretion in Women J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3208 - 3214. [Abstract] [Full Text] [PDF]

				S. S. Srouji, Y. L. Pagan, F. D'Amato, A. Dabela, Y. Jimenez, J. G. Supko, and J. E. Hall Pharmacokinetic Factors Contribute to the Inverse Relationship between Luteinizing Hormone and Body Mass Index in Polycystic Ovarian Syndrome J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1347 - 1352. [Abstract] [Full Text] [PDF]

				M. K. Murphy, J. E. Hall, J. M. Adams, H. Lee, and C. K. Welt Polycystic Ovarian Morphology in Normal Women Does Not Predict the Development of Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3878 - 3884. [Abstract] [Full Text] [PDF]

				I. E. Messinis Ovarian feedback, mechanism of action and possible clinical implications Hum. Reprod. Update, September 1, 2006; 12(5): 557 - 571. [Abstract] [Full Text] [PDF]

				C.K. Welt, Y. Jimenez, P.M. Sluss, P.C. Smith, and J.E. Hall Control of estradiol secretion in reproductive ageing Hum. Reprod., August 1, 2006; 21(8): 2189 - 2193. [Abstract] [Full Text] [PDF]

				Y. L. Pagan, S. S. Srouji, Y. Jimenez, A. Emerson, S. Gill, and J. E. Hall Inverse Relationship between Luteinizing Hormone and Body Mass Index in Polycystic Ovarian Syndrome: Investigation of Hypothalamic and Pituitary Contributions J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1309 - 1316. [Abstract] [Full Text] [PDF]

				C. K. Welt, A. E. Taylor, J. Fox, G. M. Messerlian, J. M. Adams, and A. L. Schneyer Follicular Arrest in Polycystic Ovary Syndrome Is Associated with Deficient Inhibin A and B Biosynthesis J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5582 - 5587. [Abstract] [Full Text] [PDF]

				H. M. Fraser, H. Wilson, K. D. Morris, I. Swanston, and S. J. Wiegand Vascular Endothelial Growth Factor Trap Suppresses Ovarian Function at All Stages of the Luteal Phase in the Macaque J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5811 - 5818. [Abstract] [Full Text] [PDF]

				C. K. Welt, A. Falorni, A. E. Taylor, K. A. Martin, and J. E. Hall Selective Theca Cell Dysfunction in Autoimmune Oophoritis Results in Multifollicular Development, Decreased Estradiol, and Elevated Inhibin B Levels J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3069 - 3076. [Abstract] [Full Text] [PDF]

				S. Luisi, P. Florio, F. M. Reis, and F. Petraglia Inhibins in female and male reproductive physiology: role in gametogenesis, conception, implantation and early pregnancy Hum. Reprod. Update, March 1, 2005; 11(2): 123 - 135. [Abstract] [Full Text] [PDF]

				C. K. Welt, J. E. Hall, J. M. Adams, and A. E. Taylor Relationship of Estradiol and Inhibin to the Follicle-Stimulating Hormone Variability in Hypergonadotropic Hypogonadism or Premature Ovarian Failure J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 826 - 830. [Abstract] [Full Text] [PDF]

				F. Miro and L.J. Aspinall The onset of the initial rise in follicle-stimulating hormone during the human menstrual cycle Hum. Reprod., January 1, 2005; 20(1): 96 - 100. [Abstract] [Full Text] [PDF]

				K. Dafopoulos, C.G. Kotsovassilis, S. Milingos, A. Kallitsaris, G. Galazios, E. Zintzaras, P. Sotiros, and I.E. Messinis Changes in pituitary sensitivity to GnRH in estrogen-treated post-menopausal women: evidence that gonadotrophin surge attenuating factor plays a physiological role Hum. Reprod., September 1, 2004; 19(9): 1985 - 1992. [Abstract] [Full Text] [PDF]