| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 18, 2006
Accepted on February 6, 2007
Promoter is Determined by a Negative Feedback Loop Involving Egr1 and Nab1/2
Departments of Reproductive Medicine, Neuroscience, and Medicine, and the UCSD Cancer Center, University of California, San Diego, CA 92093 and the Medical Research Service, VA San Diego Healthcare System, San Diego CA 92161
* To whom correspondence should be addressed. E-mail: mlawson{at}ucsd.edu.
The hypothalamic-pituitary-gonadal endocrine axis regulates reproduction through estrous-phase dependent release of the heterodimeric gonadotropic glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone, from the gonadotropes of the anterior pituitary. Gonadotropin synthesis and release is dependent upon pulsatile stimulation by the hypothalamic neuropeptide GnRH. Alterations in pulse frequency and amplitude alter the relative levels of gonadotropin synthesis and release. The mechanism of interpretation of GnRH pulse frequency and amplitude by gonadotropes is not understood. We have examined gene expression in L
T2 gonadotropes under various pulse regimes in a cell perifusion system by microarray and identified 1127 genes activated by tonic or pulsatile GnRH. Distinct patterns of expression are associated with each pulse frequency, but the greatest changes occur at a 60-minute inter-pulse interval or less. The immediate early gene mRNAs encoding Egr1 and Egr 2, which activate the gonadotropin luteinizing hormone beta-subunit gene promoter, are stably induced at high pulse frequency. In contrast, mRNAs for the Egr co-repressor genes Nab1 and Nab2 are stably induced at low pulse frequency. We show that Nab members inhibit Egr-mediated frequency-dependent induction of the luteinizing hormone beta-subunit promoter. This pattern of expression suggests a model of pulse frequency detection that acts by suppressing activation by Egr family members at low-frequency and allowing activation at sustained high-frequency pulses.
This article has been cited by other articles:
 |
|
 |
|
  J. Feng, M. A. Lawson, and P. Melamed A Proteomic Comparison of Immature and Mature Mouse Gonadotrophs Reveals Novel Differentially Expressed Nuclear Proteins that Regulate Gonadotropin Gene Transcription and RNA Splicing Biol Reprod, September 1, 2008; 79(3): 546 - 561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Aksglaede, R. B. Jensen, E. Carlsen, P. Kok, D. M Keenan, J. Veldhuis, N. E Skakkebaek, and A. Juul Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes. Eur. J. Endocrinol., June 1, 2008; 158(6): 803 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Haisenleder, L. L. Burger, H. E. Walsh, J. Stevens, K. W. Aylor, M. A. Shupnik, and J. C. Marshall Pulsatile Gonadotropin-Releasing Hormone Stimulation of Gonadotropin Subunit Transcription in Rat Pituitaries: Evidence for the Involvement of Jun N-Terminal Kinase But Not p38 Endocrinology, January 1, 2008; 149(1): 139 - 145. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
