help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chappell, P. E.
Right arrow Articles by Levine, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chappell, P. E.
Right arrow Articles by Levine, J. E.
Endocrinology Vol. 138, No. 10 4147-4152
Copyright © 1997 by The Endocrine Society

ARTICLES

Endocrine Defects in Mice Carrying a Null Mutation for the Progesterone Receptor Gene1

Patrick E. Chappell, John P. Lydon, Orla M. Conneely, Bert W. O’ Malley and Jon E. Levine

Department of Neurobiology and Physiology (P.E.C., J.E.L.), Northwestern University, Evanston, Illinois 60208; and Department of Cell Biology and Center for Comparative Medicine (J.P.L., O.M.C., B.W.O.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Jon E. Levine, Ph.D., Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208. E-mail: jlevine{at}nwu.edu

Mice carrying a null mutation of the progesterone receptor gene exhibit several reproductive abnormalities, including anovulation, attenuated lordotic behavior, uterine hyperplasia, and lack of mammary gland development. The hormonal correlates of these abnormalities are unknown, however, and were the focus of these studies. Serum samples from female wild-type (WT) and progesterone receptor knockout (PRKO) mice were obtained and analyzed by RIA for LH, FSH, PRL, estrogen (E2), and progesterone. Hypothalamic tissues were also processed for measurement of LHRH by RIA. Serum LH levels in PRKO mice were found to be elevated by approximately 2-fold over basal (metestrus) values in WT mice. By contrast, basal FSH levels were not different in PRKO and WT mice. Basal levels of E2 and progesterone in serum were likewise similar in the two groups, as were hypothalamic LHRH concentrations. Basal PRL levels were slightly higher in PRKO vs. WT mice. Ovariectomy of both groups of mice was accompanied by significant increases in both LH and FSH. At 5 days following ovariectomy, LH levels were elevated in both groups by 2-fold over PRKO basal and 4-fold over WT basal levels; however, by 10 days postovariectomy LH levels had continued to rise to a greater extent in PRKO mice than in WT animals. The FSH response to ovariectomy was greater for the PRKO mice at 5 days, but was no different from WT at 10 days. Of seven PRKO mice that were exposed to male odor, none exhibited preovulatory surges 3 days later, on the day of presumptive proestrus; this was in marked contrast with WT females, in which 100% exhibited robust LH surges. These results confirm the essential role of progesterone receptors in the regulation of hypothalamic and/or pituitary processes that govern gonadotropin secretion. The finding that basal LH levels are elevated in PRKO mice confirms that circulating progesterone normally conveys a significant portion of the total ovarian negative feedback control of the gonadotropin. That gonadotropin responses to ovariectomy are slightly enhanced in PRKO mice suggests that adrenal progesterone may contribute to the imposition of negative feedback control. The apparent inability of PRKO mice to respond to male odor suggests that anovulation in these mice may not be solely due to reproductive abnormalities within the ovary itself; rather, PRKO mice additionally harbor neuroendocrine defects that render them incapable of mounting normal preovulatory gonadotropin surges. It remains to be determined how the absence of PR in brain and pituitary of PRKO mice may produce this hormonal acyclicity and, conversely, how the presence of PR in brain and pituitary of WT mice may be obligatory in the generation of gonadotropin surges.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
W. Huang, M. Acosta-Martinez, and J. E. Levine
Ovarian Steroids Stimulate Adenosine Triphosphate-Sensitive Potassium (KATP) Channel Subunit Gene Expression and Confer Responsiveness of the Gonadotropin-Releasing Hormone Pulse Generator to KATP Channel Modulation
Endocrinology, May 1, 2008; 149(5): 2423 - 2432.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. J. Rickard, U. T. Iwaniec, G. Evans, T. E. Hefferan, J. C. Hunter, K. M. Waters, J. P. Lydon, B. W. O'Malley, S. Khosla, T. C. Spelsberg, et al.
Bone Growth and Turnover in Progesterone Receptor Knockout Mice
Endocrinology, May 1, 2008; 149(5): 2383 - 2390.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. J. Greives, A. O. Mason, M.-A. L. Scotti, J. Levine, E. D. Ketterson, L. J. Kriegsfeld, and G. E. Demas
Environmental Control of Kisspeptin: Implications for Seasonal Reproduction
Endocrinology, March 1, 2007; 148(3): 1158 - 1166.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
A. Romano, B. Delvoux, D.-C. Fischer, and P. Groothuis
The PROGINS polymorphism of the human progesterone receptor diminishes the response to progesterone
J. Mol. Endocrinol., February 1, 2007; 38(2): 331 - 350.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
M. Timmons, M. Tsokos, M. A. Asab, S. B. Seminara, G. C. Zirzow, C. R. Kaneski, J. D. Heiss, M. S. van der Knaap, M. T. Vanier, R. Schiffmann, et al.
Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia
Neurology, December 12, 2006; 67(11): 2066 - 2069.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
J. Lindzey, F. L Jayes, M. M Yates, J. F Couse, and K. S Korach
The bi-modal effects of estradiol on gonadotropin synthesis and secretion in female mice are dependent on estrogen receptor-{alpha}.
J. Endocrinol., October 1, 2006; 191(1): 309 - 317.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
K. A. Pooley, C. S. Healey, P. L. Smith, P. D.P. Pharoah, D. Thompson, L. Tee, J. West, C. Jordan, D. F. Easton, B. A.J. Ponder, et al.
Association of the progesterone receptor gene with breast cancer risk: a single-nucleotide polymorphism tagging approach.
Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 675 - 682.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Ko, M. C. Gieske, L. Al-Alem, Y. Hahn, W. Su, M. C. Gong, M. Iglarz, and Y. Koo
Endothelin-2 in Ovarian Follicle Rupture
Endocrinology, April 1, 2006; 147(4): 1770 - 1779.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
C. V. V. Helena, M. de Oliveira Poletini, G. L. Sanvitto, S. Hayashi, C. R. Franci, and J. A. Anselmo-Franci
Changes in {alpha}-estradiol receptor and progesterone receptor expression in the locus coeruleus and preoptic area throughout the rat estrous cycle
J. Endocrinol., February 1, 2006; 188(2): 155 - 165.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S.-K. Han, M. L. Gottsch, K. J. Lee, S. M. Popa, J. T. Smith, S. K. Jakawich, D. K. Clifton, R. A. Steiner, and A. E. Herbison
Activation of Gonadotropin-Releasing Hormone Neurons by Kisspeptin as a Neuroendocrine Switch for the Onset of Puberty
J. Neurosci., December 7, 2005; 25(49): 11349 - 11356.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
X. Qin, M. Dobarro, S. J. Bedford, S. Ferris, P. V. Miranda, W. Song, R. T. Bronson, P. E. Visconti, and J. A. Halperin
Further Characterization of Reproductive Abnormalities in mCd59b Knockout Mice: A Potential New Function of mCd59 in Male Reproduction
J. Immunol., November 15, 2005; 175(10): 6294 - 6302.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. A. Christian, J. L. Mobley, and S. M. Moenter
Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity
PNAS, October 25, 2005; 102(43): 15682 - 15687.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. S. Schneider, C. Burgess, N. C. Sleiter, L. L. DonCarlos, J. P. Lydon, B. O'Malley, and J. E. Levine
Enhanced Sexual Behaviors and Androgen Receptor Immunoreactivity in the Male Progesterone Receptor Knockout Mouse
Endocrinology, October 1, 2005; 146(10): 4340 - 4348.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. S. Reddy, D. C. Castaneda, B. W. O'Malley, and M. A. Rogawski
Anticonvulsant Activity of Progesterone and Neurosteroids in Progesterone Receptor Knockout Mice
J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 230 - 239.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. Mulac-Jericevic, J. P. Lydon, F. J. DeMayo, and O. M. Conneely
Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform
PNAS, August 19, 2003; 100(17): 9744 - 9749.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
R. Shao, E. Markstrom, P. A. Friberg, M. Johansson, and H. Billig
Expression of Progesterone Receptor (PR) A and B Isoforms in Mouse Granulosa Cells: Stage-Dependent PR-Mediated Regulation of Apoptosis and Cell Proliferation
Biol Reprod, March 1, 2003; 68(3): 914 - 921.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
P. M. Ismail, J. Li, F. J. DeMayo, B. W. O'Malley, and J. P. Lydon
A Novel LacZ Reporter Mouse Reveals Complex Regulation of the Progesterone Receptor Promoter During Mammary Gland Development
Mol. Endocrinol., November 1, 2002; 16(11): 2475 - 2489.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
A. Gumen and M. C. Wiltbank
An Alteration in the Hypothalamic Action of Estradiol Due to Lack of Progesterone Exposure Can Cause Follicular Cysts in Cattle
Biol Reprod, June 1, 2002; 66(6): 1689 - 1695.
[Abstract] [Full Text] [PDF]

Home page
 Recent Prog Horm ResHome page
O. M. Conneely, B. Mulac-Jericevic, F. DeMayo, J. P. Lydon, and B. W. O'Malley
Reproductive Functions of Progesterone Receptors
Recent Prog. Horm. Res., January 1, 2002; 57(1): 339 - 355.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. A. Sim, M. J. Skynner, and A. E. Herbison
Direct Regulation of Postnatal GnRH Neurons by the Progesterone Derivative Allopregnanolone in the Mouse
Endocrinology, October 1, 2001; 142(10): 4448 - 4453.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. L. Turgeon, G. Shyamala, and D. W. Waring
PR Localization and Anterior Pituitary Cell Populations in Vitro in Ovariectomized Wild-Type and PR-Knockout Mice
Endocrinology, October 1, 2001; 142(10): 4479 - 4485.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Amsterdam, K. Kannan, D. Givol, Y. Yoshida, K. Tajima, and A. Dantes
Apoptosis of Granulosa Cells and Female Infertility in Achondroplastic Mice Expressing Mutant Fibroblast Growth Factor Receptor 3G374R
Mol. Endocrinol., September 1, 2001; 15(9): 1610 - 1623.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. L. Turgeon and D. W. Waring
Luteinizing Hormone Secretion from Wild-Type and Progesterone Receptor Knockout Mouse Anterior Pituitary Cells
Endocrinology, July 1, 2001; 142(7): 3108 - 3115.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. B. Schwartz
Perspective: Reproductive Endocrinology and Human Health in the 20th Century--A Personal Retrospective
Endocrinology, June 1, 2001; 142(6): 2163 - 2166.
[Full Text] [PDF]

Home page
 Biol. Reprod.Home page
T. Kurita, K.-j. Lee, P. T.K. Saunders, P. S. Cooke, J. A. Taylor, D. B. Lubahn, C. Zhao, S. Mäkelä, J.-A. Gustafsson, R. Dahiya, et al.
Regulation of Progesterone Receptors and Decidualization in Uterine Stroma of the Estrogen Receptor-{{alpha}} Knockout Mouse
Biol Reprod, January 1, 2001; 64(1): 272 - 283.
[Abstract] [Full Text]

Home page
 Biol. Reprod.Home page
B. R. Rueda, I. R. Hendry, W. J. Hendry III, F. Stormshak, O.D. Slayden, and J. S. Davis
Decreased Progesterone Levels and Progesterone Receptor Antagonists Promote Apoptotic Cell Death in Bovine Luteal Cells
Biol Reprod, February 1, 2000; 62(2): 269 - 276.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
C. Ko, Y.-H. In, and O.-K. Park-Sarge
Role of Progesterone Receptor Activation in Pituitary Adenylate Cyclase Activating Polypeptide Gene Expression in Rat Ovary
Endocrinology, November 1, 1999; 140(11): 5185 - 5194.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
J. P. Lydon, G. Ge, F. S. Kittrell, D. Medina, and B. W. O'Malley
Murine Mammary Gland Carcinogenesis Is Critically Dependent on Progesterone Receptor Function
Cancer Res., September 1, 1999; 59(17): 4276 - 4284.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. E. Chappell, J. S. Schneider, P. Kim, M. Xu, J. P. Lydon, B. W. O’Malley, and J. E. Levine
Absence of Gonadotropin Surges and Gonadotropin-Releasing Hormone Self-Priming in Ovariectomized (OVX), Estrogen (E2)-Treated, Progesterone Receptor Knockout (PRKO) Mice
Endocrinology, August 1, 1999; 140(8): 3653 - 3658.
[Abstract] [Full Text]

Home page
 Endocr. Rev.Home page
J. F. Couse and K. S. Korach
Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us?
Endocr. Rev., June 1, 1999; 20(3): 358 - 417.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
S.-H. Yen and J.-T. Pan
Progesterone Advances the Diurnal Rhythm of Tuberoinfundibular Dopaminergic Neuronal Activity and the Prolactin Surge in Ovariectomized, Estrogen-Primed Rats and in Intact Proestrous Rats
Endocrinology, April 1, 1998; 139(4): 1602 - 1609.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society