The Journal of steroid biochemistry and molecular biology
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J. Steroid Biochem. Mol. Biol. · Feb 2010
Impact of aromatase inhibitors on bone health in breast cancer patients.
Following the implementation of the third generation aromatase inhibitors in the treatment algorithms for early breast cancer, special attention has been given to the influence of these drugs on bone health. Due to their potent estrogen suppression, the aromatase inhibitors anastrozole and letrozole, as well as the aromatase inactivator exemestane, enhance bone loss in postmenopausal women reflected in decreasing levels of bone mineral density. Moreover, all major phase III trials involving aromatase inhibitors in the adjuvant setting have reported increased fracture rates. ⋯ Thus, bisphosphonates have been shown to prohibit bone loss during AI therapy if used upfront. Novel treatment strategies, like antibodies against RANKL have been developed and promising preliminary results have been published from early trials. Standardized guidelines to avoid or minimize bone loss during AI therapy have been developed, in most countries involving calcium and vitamin D supplementation, as well as BMD measurements to identify patient subgroups demanding bisphosphonate therapy.
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J. Steroid Biochem. Mol. Biol. · Feb 2010
Mechanism of action of bolandiol (19-nortestosterone-3beta,17beta-diol), a unique anabolic steroid with androgenic, estrogenic, and progestational activities.
Bolandiol is a synthetic anabolic steroid that increases lean body mass and bone mineral density without significant stimulation of sex accessory glands in castrate adult male rats. Since bolandiol suppresses gonadotropins and endogenous testosterone (T) production, we investigated its mechanism of action. We compared the potency of bolandiol in vitro and in vivo with T, 5alpha-dihydrotestosterone (DHT), 19-nortestosterone (19-NT) and estradiol (E(2)). ⋯ Bolandiol also stimulated uterine weight increases in immature female rats, which were partly blocked by ICI 182,780, but it was not aromatized in vitro by recombinant human aromatase. In contrast to T, stimulation of sex accessory gland weights by bolandiol was not inhibited by concomitant treatment with the dual 5alpha-reductase inhibitor dutasteride. As bolandiol exhibits tissue selectivity in vivo, it may act via AR, PR, and/or ER, utilize alternative signaling pathway(s) or transcriptional coregulators, and/or be metabolized to a more potent selective steroid.
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J. Steroid Biochem. Mol. Biol. · Aug 2009
Induction of the adrenoleukodystrophy-related gene (ABCD2) by thyromimetics.
X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 (ALD) gene. The ABCD2 gene, its closest homolog, has been shown to compensate for ABCD1 deficiency when overexpressed. We previously demonstrated that the ABCD2 promoter contains a functional thyroid hormone response element. ⋯ Both thyromimetics trigger up-regulation of ABCD2-4 genes in HepG2 cells and X-ALD fibroblasts. Interestingly, in X-ALD fibroblasts, while T3 is associated with a transient induction of ABCD2 and ABCD3, the treatments with thyromimetics allow the induction to be maintained until 10 days. Further in vivo experiments in Abcd1 null mice with these thyromimetics should confirm the therapeutic potentialities of these molecules.
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J. Steroid Biochem. Mol. Biol. · Feb 2008
ReviewActivity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors.
SU11248 sunitinib malate sutent is a selective inhibitor of certain protein tyrosine kinases including VEGF-R types 1-3 PDGF-R-a and -b, c-kit, and RET. Its antitumor activity may result from both inhibition of angiogenesis and direct antiproliferative effects on certain tumor types. In several phase I/II/III studies, sutent was found to be effective as second and first line treatment in metastatic renal cell carcinoma (RCC). ⋯ In addition, a phase II study in multitreated women with breast cancer, sutent demonstrated a moderate activity with 16% clinical benefit. Finally, in non-small cell lung cancer (NSCLC) in patients' progressing on chemotherapy sutent was able to achieve a 10% response rate, a level of activity similar to those documented by other agents approved for lung cancer. The agent is being tested in other tumors with a modified schedule of dosage.
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J. Steroid Biochem. Mol. Biol. · Jan 2005
Case ReportsTesticular adrenal rest tumours in salt wasting congenital adrenal hyperplasia (in vivo and in vitro studies).
We describe the case of a 20-year-old patient with salt-wasting congenital adrenal hyperplasia (CAH) related to 21-hydroxylase deficiency. Bilateral craggy testicular tumours were found, requiring histological evaluation. Prior to the surgical procedure, the patient was treated with dexamethasone (he presented cortisol deficiency) and was stimulated with ACTH. ⋯ Incubation of the tumours (which could not be differentiated histologically, from Leydig tissue), with radioactive steroid precursors was carried out. The results revealed the testicular tumours were of adrenal tissue origin, associated with 21-hydroxylase deficiency. The patient's non-compliance to glucocorticoid treatment was the main cause of his hypogonadotropic hypogonadism.