Aromatase activity

Aromatase activity, and hence the capacity to synthesize estrogens, is found in a variety of tissues in the body. Gonadal sites include the ovaries in premenopausal women and the testes in men. Important extragonadal sites of aromatase activity include the placenta, chondrocytes and osteoblasts of bone, adipose tissue, muscle and brain. Aromatase plays an important... 

Cooke CM (2002) Effect of organotins on human aromatase activity in vitro. Toxicoiogy Letters, 126 121-130. 

Heidrich DD, Steckelbroek S, Klingmueller D (2001) Inhibition of human cytochrome P450 aromatase activity by butyltins. Steroids, 66 763—769. 

Of particular interest in the present context is that TBT can inhibit cytochrome-P450-based aromatase activity in both vertebrates and aquatic invertebrates (Morcillo et al. 2004, Oberdorster and McClellan-Green 2002). The conversion of testosterone to estradiol is catalyzed by aromatase, and so inhibition of the enzyme can, in principle, lead to an increase in cellular levels of testosterone. The significance of this is that many mollusks experience endocrine disruption when exposed to TBTs,... 

Effects of flavonoids on aromatase activity, an in vitro study. JSteroid Biochem Mol Biol. 57 215-23. 

Grube BJ, Eng ET, Yeh CK, Kwon A and Shiuan C. 2001. White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. J Nutr 13 3288-3293. 

Both aromatization and 5a-reductase are regulated by gonadal steroids. In mammals such as the rat, it is principally the neural aromatase activity that is upregulated by androgens acting via neural androgen receptors [1],... 

Long BJ, Tilghman SL, Yue W, Thiantanawat A, Grigoryev DN, Brodie AM (1998) The steroidal antiestrogen ICI 182,780 is an inhibitor of cellular aromatase activity. J Steroid BioChem Mol Biol 67 293-304... 

Santner SJ, Pauley RJ, Tait L (1997) Aromatase activity and expression in breast cancer and benign breast tissue stromal cells. J Clin Endocrinol Metab 82 200-208... 

Higher aromatase activity in human cerebral cortex than subcortical white matter ... 

Jimbo M, Okubo K, Toma Y, Shimizu Y, Saito H, et al. 1998. Inhibitory effects of catecholamines and maternal stress on aromatase activity in the fetal rat brain. J Obstet Gynaecol... 

Villegier AS, Salomon L, et al (2006) Monoamine oxidase inhibitors allow locomotor and rewarding responses to nicotine. Neuropsychopharmacology 31(8) 1704-1713 von Ziegler NI, Schlumpf M, et al (1991) Prenatal nicotine exposure selectively affects perinatal forebrain aromatase activity and fetal adrenal function in male rats. Brain Res Dev Brain Res 62(1) 23-31... 

Testolactone is a synthetic drug related to testosterone. It is used for palliative treatment of advanced breast cancer in postmenopausal women and in women who have had their ovaries removed. The principal action of testolactone is reported to be inhibition of steroid aromatase activity and the reduction in estrone synthesis. The most common adverse effects are nausea, vomiting, and anorexia. An advantage is that it does not cause women to develop male characteristics such as a deep voice or facial hair. 

The ovary also produces inhibin and activin. These peptides consist of several combinations of and 3 subunits and are described in greater detail later. The oc3 dimer (inhibin) inhibits FSH secretion while the 33 dimer (activin) increases FSH secretion. Studies in primates indicate that inhibin has no direct effect on ovarian steroidogenesis but that activin modulates the response to LH and FSH. For example, simultaneous treatment with activin and human FSH enhances FSH stimulation of progesterone synthesis and aromatase activity in granulosa cells. When combined with LH, activin suppressed the LH-induced progesterone response by 50% but markedly enhanced basal and LH-stimulated aromatase activity. Activin may also act as a growth factor in other tissues. The physiologic roles of these modulators are not fully understood. 

Several other aromatase inhibitors are undergoing clinical trials in patients with breast cancer. Fadrozole is an oral nonsteroidal (triazole) inhibitor of aromatase activity. These compounds appear to be as effective as tamoxifen. In addition to their use in breast cancer, aromatase inhibitors have been successfully employed as adjuncts to androgen antagonists in the treatment of precocious puberty and as primary treatment in the excessive aromatase syndrome. 

Neves MA, Dinis TC, Colombo G, Sa e Melo ML (2007). Combining computational and biochemical studies for a rationale on the anti-aromatase activity of natural polyphenols, chem med chem 2 1750-1762. 

Hecker, M., J.P. Giesy, P.D. Jones, A.M. Jooste, J.A. Carr, K.R. Solomon, E.E. Smith, G. Van Der Rraak, R.J. Kendall, and L. Du Preez (2004). Plasma sex steroid concentrations and gonadal aromatase activities in African clawed frogs (Xenopus laevis) from South Africa. Environ. Toxicol. Chem., 23(8) 1996-2007. 

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