A5028601434- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
- Cytokine Signaling Pathways and Interactions
- Drug Transport and Resistance Mechanisms
- Phytoestrogen effects and research
- Receptor Mechanisms and Signaling
- Growth Hormone and Insulin-like Growth Factors
- Retinoids in leukemia and cellular processes
- Epigenetics and DNA Methylation
- Cancer Risks and Factors
- ATP Synthase and ATPases Research
- Cancer, Lipids, and Metabolism
- Stress Responses and Cortisol
- Nuclear Receptors and Signaling
- Adipose Tissue and Metabolism
- Circadian rhythm and melatonin
- Natural product bioactivities and synthesis
- Genomics and Chromatin Dynamics
- Effects and risks of endocrine disrupting chemicals
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- TGF-β signaling in diseases
- Metabolism, Diabetes, and Cancer
- Pharmacogenetics and Drug Metabolism
- FOXO transcription factor regulation
- Renin-Angiotensin System Studies
Hudson Institute of Medical Research
2014-2024
Monash Medical Centre
2002-2020
Monash University
2006-2019
Monash Institute of Medical Research
2002-2014
Institute for Medical Research
2000-2013
Australian Regenerative Medicine Institute
2005-2013
Hudson Institute
1992-2006
St Vincents Institute of Medical Research
2004
The University of Texas Southwestern Medical Center
1995-2002
University College Dublin
1996
We present the fourth case of an adult man (29 yr old) affected by aromatase deficiency resulting from a novel homozygous inactivating mutation CYP19 (P450arom) gene. At first observation, continuing linear growth, eunuchoid body proportions, diffuse bone pain, and bilateral cryptorchidism were observed. The patient presented also complex dysmetabolic syndrome characterized insulin resistance, diabetes mellitus type 2, acanthosis nigricans, liver steatohepatitis, signs precocious...
Estrogen biosynthesis from C19steroids is catalyzed by aromatase cytochrome P450. Aromatase expressed in breast adipose tissue through the use of a distal, cytokine-responsive promoter (promoter I.4). Breast tumors, however, secrete soluble factors that stimulate expression an alternative proximal promoter, II. In other estrogenic tissues such as ovaries, transcription II requires presence Ftz-F1 homologue steroidogenic factor-1 (SF-1); tissue, does not express SF-1. We have explored...
Abstract Aldosterone synthase is a mitochondrial enzyme that catalyzes the conversion of 11-deoxycorticosterone to potent mineralocorticoid aldosterone. The gene encoding aldosterone synthase, CYP11B2, expressed in zona glomerulosa adrenal cortex. Although major physiological regulators production are angiotensin II (ANG II) and potassium (K+), mechanisms by which these compounds regulate CYP11B2 transcription unknown. Therefore we analyzed human 5′-flanking region using transient...
Background Granulosa cell tumors (GCT) of the ovary often express aromatase and synthesize estrogen, which in turn may influence their progression. Recently a specific point mutation (C134W) FOXL2 protein was identified >94% adult-type GCT it is likely to contribute development. A number genes are known be regulated by FOXL2, including aromatase/CYP19A1, but unclear direct targets whether C134W alters regulation. Recently, has been reported that forms complex with steroidogenic factor 1...
To identify biologically relevant groupings or clusters of nuclear receptors (NR) that are associated with breast neoplasia, potentially diagnostic, discriminant prognostic value, we quantitated mRNA expression levels all 48 members the human NR superfamily by TaqMan low-density array analysis in 116 curated tissue samples, including pre- and postmenopausal normal both ERα+ ERα− tumor tissue. In addition, have determined independent cohorts tamoxifen-treated samples. There were differences...
11beta-Hydroxylase (hCYP11B1) and aldosterone synthase (hCYP11B2) are closely related isozymes with distinct roles in cortisol production respectively. Aldosterone catalyzes the final step biosynthesis is expressed only zona glomerulosa of normal adrenal. reaction at higher levels fasciculata. The mechanisms causing differential expression these genes not well defined. Herein, we demonstrate contrasting for orphan receptor steroidogenic factor-1 (SF-1) regulation human (h) CYP11B1 hCYP11B2....
The present study explores the possibility of local de novo aldosterone production in normal and failing hearts (human mouse) regulation such putative cardiac steroidogenesis. Total RNA was isolated from human tissue taken at time transplantation, obtained autopsy, pressure-overloaded mouse hearts. Vascular smooth muscle cells artery vein were also analyzed. reverse transcribed probed with specific primers for side-chain cleavage enzyme (CYP11A), 3β-hydroxysteroid dehydrogenase, synthase...
Local synthesis of estrogens within breast adipose tissue by cytochrome P450 aromatase contributes to the growth postmenopausal cancers. One major stimulators expression in is prostaglandin E(2) (PGE(2)) derived from tumorous epithelium and/or infiltrating macrophages. Recently, orphan nuclear receptor, liver receptor homologue-1 (LRH-1), has also been shown regulate tissue. We therefore examined of, and correlations between, LRH-1 mRNA a panel carcinoma tissues adjacent was low normal but...
Summary Background Descriptions of new cases human aromatase deficiency are useful for a better understanding male oestrogen pathophysiology, as some aspects remain controversial. Objective To present case an adult man affected by deficiency, along with description clinical phenotype, and hormonal genetic analysis. Design Case report study. Patient A 25‐year‐old continuing linear growth, eunuchoid body habitus diffuse bone pain. Measurements Amplification sequencing all coding exons their...
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in patients is correlated with improved survival outcomes renal, prostate, breast small cell lung cancer. Previous studies demonstrate Type I (AT1R) linked pathogenesis, unbiased analysis gene-expression identifying significant...
Aromatase converts testicular androgens to estrogens, which are essential for male fertility. expression in testis occurs via transcription from promoter II, and requires the presence of a nuclear receptor half-site that binds orphan steroidogenic factor-1 [SF-1 (nuclear 5A1)] mediate basal (in part) cAMP-induced transcription. We hypothesized liver homolog-1 (LRH-1) 5A2), closely related SF-1, could also play role regulating aromatase testis. demonstrate LRH-1 adult rat immature mouse...
Background Liver Receptor Homolog 1 (LRH-1, NR5A2) is an orphan nuclear receptor that over-expressed in cancers tissues such as the breast, colon and pancreas. LRH-1 plays important roles embryonic development, steroidogenesis cholesterol homeostasis. In tumor cells, induces proliferation cell cycle progression. High expression demonstrated breast cancers, positively correlating with ERα status aromatase activity. dependent cellular mechanisms cancer epithelial cells are poorly defined....
Flavonoids are secondary metabolites abundantly present in commonly consumed fruits and vegetables. They possess diverse properties such as anti-inflammatory, anti-oxidant anti-cancer. Epidemiologic studies suggest that an enrich flavonoids diet is linked to a decreased risk of breast cancer. These protective due the alteration numerous signalling pathways involved cancer-related phenomena inflammation proliferation. Human clinical trials examining effect supplementation some on disease...
Abstract Macrophage migration inhibitory factor (MIF) has a key role in regulation of innate and adaptive immunity is implicated sepsis, tumorigenesis, autoimmune disease. MIF deficiency or immunoneutralization leads to protection against fatal endotoxic, exotoxic, infective shock, anti-inflammatory effects other experimental models inflammatory We report novel regulatory type 1 IL-1R p55 TNFR expression function. Compared with wild-type cells, MIF-deficient cells were hyporesponsive IL-1-...