| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
5-4 Isomerase Gene: Activation by Prolactin
Vanderbilt University School of Medicine (F.A.F., M.H.M.)
Departments of Obstetrics/Gynecology and Cell Biology Nashville,
Tennessee 37232
Institute for Biomedical Research (B.G.)
Georg-Speyer-Haus Frankfurt, Germany
Altered PRL levels are associated with infertility
in women. Molecular targets at which PRL elicits these effects have yet
to be determined. These studies demonstrate transcriptional regulation
by PRL of the gene encoding the final enzymatic step in progesterone
biosynthesis: 3ß-hydroxysteroid
dehydrogenase/
5-4 isomerase (3ß-HSD). A
9/9 match with the consensus Stat5 response element was identified at
-110 to -118 in the human Type II 3ß-HSD promoter. 3ß-HSD
chloramphenicol acetyltransferase (CAT) reporter constructs containing
either an intact or mutated Stat5 element were tested for PRL
activation. Expression vectors for Stat5 and the PRL receptor were
cotransfected with a -300 
+45 3ß-HSD CAT reporter construct into
HeLa cells, which resulted in a 21-fold increase in reporter activity
in the presence of PRL. Promoter activity showed an increased response
with a stepwise elevation of transfected Stat5 expression or by
treatment with increasing concentrations of PRL (max, 250 ng/ml). This
effect was dramatically reduced when the putative Stat5
response element was removed by 5'-deletion of the promoter or by
the introduction of a 3-bp mutation into critical nucleotides in
the element. Furthermore, 32P-labeled
promoter fragments containing the Stat5 element were shifted in
electrophoretic mobility shift assay experiments using nuclear
extracts from cells treated with PRL, and this complex was supershifted
with antibodies to Stat5. These results demonstrate that PRL has the
ability to regulate expression of a key human enzyme gene (type II
3ß-HSD) in the progesterone biosynthetic pathway, which is essential
for maintaining pregnancy.
This article has been cited by other articles:
 |
|
 |
|
  H. A. LaVoie and S. R. King Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B Experimental Biology and Medicine, August 1, 2009; 234(8): 880 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bachelot and N. Binart Reproductive role of prolactin Reproduction, February 1, 2007; 133(2): 361 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Stocco, C. Telleria, and G. Gibori The Molecular Control of Corpus Luteum Formation, Function, and Regression Endocr. Rev., February 1, 2007; 28(1): 117 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Martin, H. Taniguchi, N. M. Robert, J. Simard, J. J. Tremblay, and R. S. Viger GATA Factors and the Nuclear Receptors, Steroidogenic Factor 1/Liver Receptor Homolog 1, Are Key Mutual Partners in the Regulation of the Human 3{beta}-Hydroxysteroid Dehydrogenase Type 2 Promoter Mol. Endocrinol., September 1, 2005; 19(9): 2358 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family Endocr. Rev., June 1, 2005; 26(4): 525 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Martin and J. J. Tremblay The Human 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Type 2 Promoter Is a Novel Target for the Immediate Early Orphan Nuclear Receptor Nur77 in Steroidogenic Cells Endocrinology, February 1, 2005; 146(2): 861 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Payne and D. B. Hales Overview of Steroidogenic Enzymes in the Pathway from Cholesterol to Active Steroid Hormones Endocr. Rev., December 1, 2004; 25(6): 947 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Feltus, W. J. Kovacs, W. Nicholson, C. M. Silva, S. K. Nagdas, N. A. Ducharme, and M. H. Melner Epidermal Growth Factor Increases Cortisol Production and Type II 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4-Isomerase Expression in Human Adrenocortical Carcinoma Cells: Evidence for a Stat5-Dependent Mechanism Endocrinology, May 1, 2003; 144(5): 1847 - 1853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frasor, K. Park, M. Byers, C. Telleria, T. Kitamura, L.-y. Yu-Lee, J. Djiane, O.-K. Park-Sarge, and G. Gibori Differential Roles for Signal Transducers and Activators of Transcription 5a and 5b in PRL Stimulation of ER{alpha} and ER{beta} Transcription Mol. Endocrinol., December 1, 2001; 15(12): 2172 - 2181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Fleenor and M. Freemark Prolactin Induction of Insulin Gene Transcription: Roles of Glucose and Signal Transducer and Activator of Transcription 5 Endocrinology, July 1, 2001; 142(7): 2805 - 2810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Peters, E. T. Maizels, M. C. Robertson, R. P.C. Shiu, M. S. Soloff, and M. Hunzicker-Dunn Induction of Relaxin Messenger RNA Expression in Response to Prolactin Receptor Activation Requires Protein Kinase C {delta} Signaling Mol. Endocrinol., April 1, 2000; 14(4): 576 - 590. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. B. Ehret, P. Reichenbach, U. Schindler, C. M. Horvath, S. Fritz, M. Nabholz, and P. Bucher DNA Binding Specificity of Different STAT Proteins. COMPARISON OF IN VITRO SPECIFICITY WITH NATURAL TARGET SITES J. Biol. Chem., February 23, 2001; 276(9): 6675 - 6688. [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 |
