This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited 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 Gardner, D. B. Articles by Miller, W. L. Search for Related Content PubMed PubMed Citation Articles by Gardner, D. B. Articles by Miller, W. L.

Estradiol Induces and Hyperglycosylates the Receptor for Ovine Gonadotropin-Releasing Hormone¹

Department of Biochemistry, North Carolina State University, Raleigh, North Carolina 27695-7622

Address all correspondence and requests for reprints to: Dr. William L. Miller, Department of Biochemistry, Box 7622, North Carolina State University, Raleigh, North Carolina 27695-7622.

The crucial first link between GnRH and its pleiotropic stimulation of the reproductive system is its receptor (GnRHRec). In mammals, 17ß-estradiol is a major regulator of GnRH action, and part of its regulation occurs at the level of the GnRHRec. In ovine pituitary cultures, estradiol simultaneously increases GnRHRec and GnRH-stimulated LH secretion (the LH response), but after 6–15 h the effect of estradiol becomes paradoxical, and the LH response rapidly decreases to control levels (by 24 h), whereas GnRHRec remains elevated. A preliminary study used photoaffinity labeling of the GnRHRec to show that estradiol can induce 38- and 43-kDa GnRHRec. The photoaffinity technique has been used here to 1) further investigate estradiol-mediated induction of GnRHRec, 2) define the nature of the different sized GnRHRecs, and 3) determine whether the larger size is related to degradation of the LH response. The effect of estradiol is compared with that of inhibin, which only induces the 38-kDa GnRHRec and always increases the LH response to GnRH treatment. Receptors for GnRH in ovine pituitary cultures were photoaffinity labeled with [¹²⁵I](azidobenzoyl-D-Lys⁶-des-Gly¹⁰)-GnRH-N-ethylamide and analyzed by SDS-PAGE. Treatment with estradiol or inhibin for 6–24 h induced a 38-kDa GnRHRec only. Further treatment with estradiol (>24 h), but not inhibin, shifted the apparent M_r of the GnRHRec to 43 kDa. Phosphatase treatment did not reverse this apparent M_r change. Analysis of receptor glycosylation using N-glycosidase F or tunicamycin showed that the 43-kDa GnRHRec was a hyperglycosylated form of the 38-kDa GnRHRec. The 38-kDa GnRHRec, in turn, was a glycosylated form of the 29-kDa GnRHRec. The studies presented here define several glycosylated intermediates of the ovine GnRHRec that are induced by estradiol and/or inhibin. The function of estrogen-mediated hyperglycosylation is unclear, but kinetic studies dissociate it from degeneration of the LH response to GnRH.

This article has been cited by other articles:

				C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]

				F.-P. Yen, Y.-H. Lee, C.-L. He, J.-D. Huang, L.-T. Sun, S. Dufour, and C.-F. Chang Estradiol-17{beta} Triggers Luteinizing Hormone Release in the Protandrous Black Porgy (Acanthopagrus schlegeli Bleeker) Through Multiple Interactions with Gonadotropin-Releasing Hormone Control Biol Reprod, January 1, 2002; 66(1): 251 - 257. [Abstract] [Full Text]