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01 August 2005

Estrogen Signaling Is Conserved During Evolution Enhancing Its Biomedical Significance.

Kirk Mantione

Med Sci Monit 2005; 11(8): LE5-5 :: ID: 202499


Dear Editor, The term estrogen includes thirty hormones, of which the mostknown are estriol, estrone, and estradiol. In females they are produced primarily in the ovaries [1].Besides their well established actions on reproductive functions, estrogens exert a variety of actionson many regions of the nervous system that influences cognition, pain mechanisms, fine motor skills,mood as well as a susceptibility to seizures [2,3]. Estrogen hormones are produced in males as well [2,3].The role it plays in men is somewhat unclear unless it is viewed as another chemical messenger transcendingits role in reproduction. This last insight appears to be true since this signaling family, includinga mammalian-like estrogen receptor exhibiting high sequence identity with its human counterpart, is foundin invertebrates [4-7]. In these reports 17ss-estradiol was identified in invertebrate neural tissueswhere it was shown to be coupled to nitric oxide production by constitutive nitric oxide synthase. Additionally,the investigators found this last phenomenon was associated with estrogen cell surface receptors, therebyidentifying a non-genomic role for these signaling molecules. Since this signaling was found in neuraltissues the authors went on to demonstrate that estrogen participates in signaling initiating microglialdown regulation. Thus it would appear estrogen is involved in activities that can be identified as non-reproductive.Furthermore, given nitric oxide's involvement in cell growth/cancer a link is established between estrogenand neoplastic growths (see [3,8]). The history of neurobiology has repeatedly demonstrated the valueof invertebrates as model and economical systems. This now is true for examining estrogen signaling inorganisms that evolved hundreds of millions of years ago [4,9,10]. Interestingly, not only is estrogensignaling conserved but its function in reproductive, neural, and immune activities as well [4,5,11-13].Any perturbation of estrogen signaling (i.e. enhancing or diminishing the signal) could dramaticallyimpact the health of an animal. Estrogen mimicking is present in the environment not only impacting onthe development of animals but also implicated in changes to gametes [14]. The significance of this isthat this chemical messenger must be meeting an important biological requirement that impacts health.References: 1. Jones DA, Cho JJ, Salamon E, Stefano GB: Risk factors for breast cancer and the prognosisof African American women: estrogen's role. Med Sci Monit, 2003; 9: RA110-RA118 2. Cho JJ, Cadet P, SalamonE et al: The nongenomic protective effects of estrogen on the male cardiovascular system: clinical andtherapeutic implications in aging men. Med Sci Monit, 2003; 9: RA63-RA68 3. Cho JJ, Ianucci FA, FraileM et al: The role of estrogen in neuroprotection: Implications for neurodegenerative diseases. NeuroendocrinologyLetters, 2003; 24: 141-47 4. Stefano GB, Cadet P, Mantione K et al: Estrogen Signaling at the Cell SurfaceCoupled to Nitric Oxide Release in Mytilus edulis Nervous System. Endocrinology, 2003; 144: 1234-40 5.Stefano GB, Zhu W, Mantione K et al: 17-b-estradiol down regulates ganglionic microglial cells via nitricoxide release: Presence of a fragment for estrogen receptor b. Neuroendocrinology Letters, 2003; 24:130-36 6. Stefano GB: Estrogen Genomic and Nongenomic Signaling Processes May Really Be Working In Harmony.Neuroendocrinology Letters, 2003; 24: 128-29 7. Zhu W, Mantione K, Jones D et al: The Presence of 17-bestradiol in Mytilus edulis Gonadal Tissues: Evidence for Estradiol Isoforms. Neuroendocrinology Letters,2003; 24: 137-40 8. Rasmussen M, Zhu W, Tonnesen J et al: Effects of morphine on tumour growth. NeuroendocrinologyLetters, 2002; 23: 193-98 9. Di Cosmo A, Di Cristo C, Paolucci M: A estradiol-17beta receptor in thereproductive system of the female of Octopus vulgaris: characterization and immunolocalization. Mol ReprodDev, 2002; 61: 367-75 10. Thornton JW, Need E, Crews D: Resurrecting the ancestral steroid receptor:ancient origin of estrogen signaling. Science, 2003; 301: 1714-17 11. Canesi L, Ciacci C, Betti M etal: Rapid effects of 17beta-estradiol on cell signaling and function of Mytilus hemocytes. Gen Comp Endocrinol,2004; 136: 58-71 12. Matsumoto T, Osada M, Osawa Y, Mori K: Gonadal estrogen profile and immunohistochemicallocalization of steroidogenic enzymes in the oyster and scallop during sexual maturation. Comp BiochemPhysiol B Biochem Mol Biol, 1997; 118: 811-17 13. Osada M, Tawarayama H, Mori K: Estrogen synthesis inrelation to gonadal development of Japanese scallop, Patinopecten yessoensis: gonadal profile and immunolocalizationof P450 aromatase and estrogen. Comp Biochem Physiol B Biochem Mol Biol, 2004; 139: 123-28 14. Nice HE,Morritt D, Crane M, Thorndyke M: Long-term and transgenerational effects of nonylphenol exposure at akey stage in the development of Crassostrea gigas. Possible endocrine disruption? Marine Ecology ProgressSeries, 2003; 256: 293-300.

Keywords: Animals, Biomedical Research, Estrogens - metabolism, Evolution, Molecular, Signal Transduction, Animals, Biomedical Research, Estrogens - metabolism, Evolution, Molecular, Signal Transduction


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750