Origins of the Field of Molecular Endocrinology: A Personal Perspective

Published on Oct 3, 2016in Molecular Endocrinology3.628
· DOI :10.1210/ME.2016-1132
Bert W. O'Malley115
Estimated H-index: 115
  • References (14)
  • Citations (3)
#1David M. Lonard (BCM: Baylor College of Medicine)H-Index: 31
#2Bert W. O'Malley (BCM: Baylor College of Medicine)H-Index: 115
The nuclear receptor superfamily includes transcription factors that transduce steroid, thyroid and retinoid hormones and other ligands in conjunction with coregulators. To date, over 350 coregulators have been reported in the literature, and advances in proteomic analyses of coregulator protein complexes have revealed that a far greater number of coregulator-interacting proteins also exist. Coregulator dysfunction has been implicated in diverse pathological states, genetic syndromes and cancer....
160 CitationsSource
#1David M. Lonard (BCM: Baylor College of Medicine)H-Index: 31
#2Rainer B. Lanz (BCM: Baylor College of Medicine)H-Index: 28
Last. Bert W. O'Malley (BCM: Baylor College of Medicine)H-Index: 11
view all 3 authors...
Nuclear receptor (NR) coregulators (coactivators and corepressors) are essential elements in regulating nuclear receptor-mediated transcription. In a little more than a decade since their discovery, these proteins have been studied mechanistically and reveal that the regulation of transcription is a highly controlled and complex process. Because of their central role in regulating NR-mediated transcription and in coordinating intercompartmental metabolic processes, disruptions in coregulator bio...
241 CitationsSource
#1David M. Lonard (BCM: Baylor College of Medicine)H-Index: 31
#2Bert W. O'Malley (BCM: Baylor College of Medicine)H-Index: 11
About 200 coactivators play a central role in promoting gene expression mediated by nuclear receptors. This diverse group of proteins are key integrators of signals from steroid hormones and have been implicated in cancer and other diseases.
268 CitationsSource
#1Sergio A. Onate (BCM: Baylor College of Medicine)H-Index: 18
#1Sergio A. Onate (BCM: Baylor College of Medicine)H-Index: 5
Last. Bert W. O'Malley (BCM: Baylor College of Medicine)H-Index: 21
view all 4 authors...
A yeast two-hybrid system was used to identify a protein that interacts with and enhances the human progesterone receptor (hPR) transcriptional activity without altering the basal activity of the promoter. Because the protein stimulated transactivation of all the steroid receptors tested, it has been termed steroid receptor coactivator-1 (SRC-1). Coexpression of SRC-1 reversed the ability of the estrogen receptor to squelch activation by hPR. Also, the amino terminal truncated form of SRC-1 acte...
2,150 CitationsSource
#1Aria Baniahmad (BCM: Baylor College of Medicine)H-Index: 6
#1Aria Baniahmad (BCM: Baylor College of Medicine)H-Index: 27
Last. Bert W. O'Malley (BCM: Baylor College of Medicine)H-Index: 115
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The C terminus of nuclear hormone receptors is a complex structure that contains multiple functions. We are interested in the mechanism by which thyroid hormone converts its receptor from a transcriptional silencer to an activator of transcription. Both regulatory functions are localized in the ligand binding domain of this receptor superfamily member. In this study, we have identified and characterized several functional domains within the ligand binding domain of the human thyroid hormone rece...
237 CitationsSource
#1V. Craig Jordan (UW: University of Wisconsin-Madison)H-Index: 72
#2Erik Phelps (UW: University of Wisconsin-Madison)H-Index: 1
Last. J. Urban Lindgren (KI: Karolinska Institutet)H-Index: 1
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The effects of the antiestrogens tamoxifen and keoxifene on the bone density of intact and ovariectomized female rats were determined after 4 months of therapy. The antiestrogens did not cause a decrease in bone density in intact animals, although uterine wet weight did decrease. Ovariectomy caused an increase in body weight (25%) and a significant decrease in femur density (P<0.01). Antiestrogens did not further decrease the bone density of ovariectomized rats but rather helped to maintain bone...
304 CitationsSource
#2E. UbedaH-Index: 1
Last. Ana I. EsquifinoH-Index: 34
view all 7 authors...
In order to study the possible role on prolactin secretion of the catecholamines present in ectopic pituitaries, female rats bearing an anterior pituitary graft under the kidney capsule since day 30 of life and their sham-operated controls, were sacrificed at 1,2, 4, 7, 15, 30, 45 and 60 days after the operation. Data obtained showed a significant increase in plasma prolactin levels in grafted rats versus controls from the 4th day on after the grafting (p
8 CitationsSource
#1S. Green (French Institute of Health and Medical Research)H-Index: 25
#1Stephen Green (French Institute of Health and Medical Research)H-Index: 30
Last. Pierre Chambon (French Institute of Health and Medical Research)H-Index: 197
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We have cloned and sequenced the complete complementary DNA of the oestrogen receptor (ER) present in the breast cancer cell line MCF-7. The expression of the ER cDNA in HeLa cells produces a protein that has the same relative molecular mass and binds oestradiol with the same affinity as the MCF-7 ER. There is extensive homology between the ER and the erb-A protein of the oncogenic avian erythroblastosis virus.
2,003 CitationsSource
#1Stanley M. Hollenberg (UCSD: University of California, San Diego)H-Index: 13
#2Cary Weinberger (HHMI: Howard Hughes Medical Institute)H-Index: 13
Last. Ronald M. Evans (HHMI: Howard Hughes Medical Institute)H-Index: 184
view all 9 authors...
Identification of complementary DNAs encoding the human glucocorticoid receptor predicts two protein forms, of 777 (α) and 742 (β) amino acids, which differ at their carboxy termini. The proteins contain a cysteine/lysine/arginine-rich region which may define the DNA-binding domain. Pure radiolabelled glucocorticoid receptor, synthesized in vitro, is immuno-reactive and possesses intrinsic steroid-binding activity characteristic of the native glucocorticoid receptor.
1,523 CitationsSource
#1Roger L. Miesfeld (UCSF: University of California, San Francisco)H-Index: 32
#2Sam Okret (UCSF: University of California, San Francisco)H-Index: 48
Last. Keith R. Yamamoto (UCSF: University of California, San Francisco)H-Index: 79
view all 6 authors...
The effects of steroid hormones are mediated by intracellular hormone-specific receptor proteins; the interaction between the hormone and its receptor increases the affinity of the receptor for nuclear binding sites, thereby modulating the expression of specific genes. The glucocorticoid receptor is a soluble protein of relative molecular mass (Mr) 94,000 (94K), present at a low relative abundance (less than or equal to 0.01%); it has been purified to near-homogeneity, and specific antisera and ...
242 CitationsSource
Cited By3
#1Yue Zhu (University of South China)
#2Xu Yao (University of South China)
Last. Xing Zheng (University of South China)H-Index: 9
view all 7 authors...
Chrysin, a flavonoid, has played a great role in the fields of anticancer, antibacterial, and antiviral drug discovery. A large number of chrysin derivatives have been synthesized recently. The flu...
#1Peter J. Fuller (Hudson Institute of Medical Research)H-Index: 46
#2Jun Yang (Hudson Institute of Medical Research)H-Index: 9
Last. Morag J. Young (Hudson Institute of Medical Research)H-Index: 31
view all 3 authors...
Abstract The cellular response to aldosterone is mediated by the mineralocorticoid receptor (MR). This response is best characterized in the renal epithelia with control of sodium and water homeostasis. However, the MR binds more than one ligand and has wide tissue distribution with multiple roles in cardiovascular function, immune cell signaling, neuronal fate and adipocyte differentiation. This chapter will provide a review of MR structure and function, and an analysis of the critical interact...
2 CitationsSource
#1Peter J. Fuller (Monash University)H-Index: 46
#2Jun Yang (Monash University)H-Index: 1
Last. Morag J. Young (Monash University)H-Index: 31
view all 3 authors...
: The cloning of the mineralocorticoid receptor (MR) 30 years ago was the start of a new era of research into the regulatory processes of MR signalling at target genes in the distal nephron, and subsequently in many other tissues. Nuclear receptor (NR) signalling is modified by interactions with coregulatory proteins that serve to enhance or inhibit the gene transcriptional responses. Over 400 coregulatory proteins have been described for the NR super family, many with functional roles in signal...
21 CitationsSource