Extra-gonadal Sites of Estrogen Biosynthesis and Function

Overview

Journal BMB Rep

Specialties Biochemistry
Molecular Biology

Date 2016 Aug 18

PMID 27530684

Citations 80

Authors

Radwa Barakat

Oliver Oakley

Heehyen Kim

Jooyoung Jin

CheMyong Jay Ko

Affiliations

Soon will be listed here.

Abstract

Estrogens are the key hormones regulating the development and function of reproductive organs in all vertebrates. Recent evidence indicates that estrogens play important roles in the immune system, cancer development, and other critical biological processes related to human well-being. Obviously, the gonads (ovary and testis) are the primary sites of estrogen synthesis, but estrogens synthesized in extra- gonadal sites play an equally important role in controlling biological activities. Understanding non-gonadal sites of estrogen synthesis and function is crucial and will lead to therapeutic interventions targeting estrogen signaling in disease prevention and treatment. Developing a rationale targeting strategy remains challenging because knowledge of extra-gonadal biosynthesis of estrogens, and the mechanism by which estrogen activity is exerted, is very limited. In this review, we will summarize recent discoveries of extra-gonadal sites of estrogen biosynthesis and their local functions and discuss the significance of the most recent novel discovery of intestinal estrogen biosynthesis. [BMB Reports 2016; 49(9): 488-496].

Citing Articles

Acute Exposure to Ozone Affects Circulating Estradiol Levels and Gonadotropin Gene Expression in Female Mice.

Rousselle D, Silveyra P Int J Environ Res Public Health. 2025; 22(2).

PMID: 40003448 PMC: 11855596. DOI: 10.3390/ijerph22020222.

Identification and validation of Novel Estrogen Biosynthesis Biomarkers in Sinonasal Inverted Papilloma.

Yang Y, Yu S, Liao J, Lin Y Int J Med Sci. 2025; 22(1):158-169.

PMID: 39744163 PMC: 11659834. DOI: 10.7150/ijms.101753.

The interaction of BDNF with estrogen in the development of hypertension and obesity, particularly during menopause.

Zhang Z, He Z, Pan J, Yuan M, Lang Y, Wei X Front Endocrinol (Lausanne). 2024; 15:1384159.

PMID: 39655343 PMC: 11625588. DOI: 10.3389/fendo.2024.1384159.

17β-Estradiol Stimulates Oxidative Stress Components and Thyroid Specific Genes in Porcine Thyroid Follicular Cells: Potential Differences Between Sexes.

Stepniak J, Karbownik-Lewinska M Cells. 2024; 13(21.

PMID: 39513876 PMC: 11545819. DOI: 10.3390/cells13211769.

Rapid and local neuroestrogen synthesis supports long-term potentiation of hippocampal Schaffer collaterals-cornu ammonis 1 synapse in ovariectomized mice.

Maroteaux M, Noccioli C, Daniel J, Schrader L J Neuroendocrinol. 2024; 36(12):e13450.

PMID: 39351868 PMC: 11646664. DOI: 10.1111/jne.13450.

References

Ishunina T, van Beurden D, van der Meulen G, Unmehopa U, Hol E, Huitinga I . Diminished aromatase immunoreactivity in the hypothalamus, but not in the basal forebrain nuclei in Alzheimer's disease. Neurobiol Aging. 2004; 26(2):173-94. DOI: 10.1016/j.neurobiolaging.2004.03.010. View

Jung C, Hugot J, Barreau F . Peyer's Patches: The Immune Sensors of the Intestine. Int J Inflam. 2010; 2010:823710. PMC: 3004000. DOI: 10.4061/2010/823710. View

Kaludjerovic J, Ward W . The Interplay between Estrogen and Fetal Adrenal Cortex. J Nutr Metab. 2012; 2012:837901. PMC: 3321452. DOI: 10.1155/2012/837901. View

Colciago A, Celotti F, Pravettoni A, Mornati O, Martini L, Negri-Cesi P . Dimorphic expression of testosterone metabolizing enzymes in the hypothalamic area of developing rats. Brain Res Dev Brain Res. 2005; 155(2):107-16. DOI: 10.1016/j.devbrainres.2004.12.003. View

Nelson L, Bulun S . Estrogen production and action. J Am Acad Dermatol. 2001; 45(3 Suppl):S116-24. DOI: 10.1067/mjd.2001.117432. View

Cleland W, Mendelson C, Simpson E . Aromatase activity of membrane fractions of human adipose tissue stromal cells and adipocytes. Endocrinology. 1983; 113(6):2155-60. DOI: 10.1210/endo-113-6-2155. View

Bulun S, Price T, Aitken J, Mahendroo M, Simpson E . A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab. 1993; 77(6):1622-8. DOI: 10.1210/jcem.77.6.8117355. View

Broughton B, Miller A, Sobey C . Endothelium-dependent relaxation by G protein-coupled receptor 30 agonists in rat carotid arteries. Am J Physiol Heart Circ Physiol. 2010; 298(3):H1055-61. DOI: 10.1152/ajpheart.00878.2009. View

Hemsell D, GRODIN J, Brenner P, Siiteri P, MACDONALD P . Plasma precursors of estrogen. II. Correlation of the extent of conversion of plasma androstenedione to estrone with age. J Clin Endocrinol Metab. 1974; 38(3):476-9. DOI: 10.1210/jcem-38-3-476. View

10.

Gao H, Bryzgalova G, Hedman E, Khan A, Efendic S, Gustafsson J . Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol Endocrinol. 2006; 20(6):1287-99. DOI: 10.1210/me.2006-0012. View

11.

Karas R, Patterson B, Mendelsohn M . Human vascular smooth muscle cells contain functional estrogen receptor. Circulation. 1994; 89(5):1943-50. DOI: 10.1161/01.cir.89.5.1943. View

12.

Cesinaro A, Roncati L, Maiorana A . Estrogen receptor alpha overexpression in multinucleate cell angiohistiocytoma: new insights into the pathogenesis of a reactive process. Am J Dermatopathol. 2010; 32(7):655-9. DOI: 10.1097/DAD.0b013e3181d3ca49. View

13.

Slominski A, Wortsman J . Neuroendocrinology of the skin. Endocr Rev. 2000; 21(5):457-87. DOI: 10.1210/edrv.21.5.0410. View

14.

Tuddenham S, Sears C . The intestinal microbiome and health. Curr Opin Infect Dis. 2015; 28(5):464-70. PMC: 4643846. DOI: 10.1097/QCO.0000000000000196. View

15.

Gaudet H, Cheng S, Christensen E, Filardo E . The G-protein coupled estrogen receptor, GPER: The inside and inside-out story. Mol Cell Endocrinol. 2015; 418 Pt 3:207-19. DOI: 10.1016/j.mce.2015.07.016. View

16.

Relman D . Gut microbiota: How to build healthy growth-promoting gut communities. Nat Rev Gastroenterol Hepatol. 2016; 13(7):379-80. DOI: 10.1038/nrgastro.2016.74. View

17.

Salem M . Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy. 2004; 3(1):97-104. DOI: 10.2174/1568010043483944. View

18.

Xu Y, Nedungadi T, Zhu L, Sobhani N, Irani B, Davis K . Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011; 14(4):453-65. PMC: 3235745. DOI: 10.1016/j.cmet.2011.08.009. View

19.

Nicol M, Papacleovoulou G, Evans D, Penning T, Strachan M, Advani A . Estrogen biosynthesis in human H295 adrenocortical carcinoma cells. Mol Cell Endocrinol. 2008; 300(1-2):115-20. PMC: 2673546. DOI: 10.1016/j.mce.2008.10.032. View

20.

Ben Mkaddem S, Christou I, Rossato E, Berthelot L, Lehuen A, Monteiro R . IgA, IgA receptors, and their anti-inflammatory properties. Curr Top Microbiol Immunol. 2014; 382:221-35. DOI: 10.1007/978-3-319-07911-0_10. View