Expression of Estrogen Receptors in Human Corpus Cavernosum and Male Urethra

Estrogen, largely produced in testis and adrenal gland, may play important roles in male reproduction. Most of the effects of estrogens are mediated by binding of estrogen to one or both of the two estrogen receptor (ER) subtypes α and β. Recently, they have been described in testis, prostate, and efferent ducts, mostly in rodents. The goal of this study was to prove the evidence of ERs in human corpus cavernosum and male urethra, exploring the protein expression of these receptors by immunohistochemistry. Corpus cavernosum and corpus spongiosum smooth muscle was immunoreactive for the androgen receptor (AR), ERα, and strongly for ERβ. Endothelial cells were negative for AR, sporadically positive for ERα, and positive for ERβ. Urethral epithelium showed strong nuclear expression of AR, predominantly in the basal cell layer, and nuclear expression of ERα in the intermediate cells. ERβ was highly expressed in almost all urethral nuclei and, much more weakly, in cytoplasm. Progesterone receptor (PGR) was negative in all cases and all tissues. These results represent the first report that ERα and particularly ERβ are regularly expressed in human penile tissue.

[1]  A. Kitabatake,et al.  Evidence for a Potential Role of Estrogen in the Penis: Detection of Estrogen Receptor-α and -β Messenger Ribonucleic Acid and Protein , 2002 .

[2]  Mahlon D. Johnson,et al.  Immunohistochemical Localization of Carboxypeptidases D, E, and Z in Pituitary Adenomas and Normal Human Pituitary , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[3]  Mark J. Evans,et al.  Estrogen Receptors (cid:1) and (cid:2) Have Similar Activities in Multiple Endothelial Cell Pathways , 2002 .

[4]  S. Chu,et al.  17β-Estradiol Up-Regulates Vascular Endothelial Growth Factor Receptor-2 Expression in Human Myometrial Microvascular Endothelial Cells: Role of Estrogen Receptor-α and -β , 2002 .

[5]  R. Karas,et al.  The protective effects of estrogen on the cardiovascular system. , 2002, The New England journal of medicine.

[6]  D. Russell,et al.  Expression of the androgen receptor and 5α-reductase type 2 in the developing human fetal penis and urethra , 2002, Cell and Tissue Research.

[7]  C. Schneeberger,et al.  Production and actions of estrogens. , 2002, The New England journal of medicine.

[8]  J. Gustafsson,et al.  Co-localization of androgen receptor with estrogen receptor beta in the lower urinary tract of the male rat. , 2001, The Journal of urology.

[9]  K. Williams,et al.  Estrogen receptor beta, but not estrogen receptor alpha, is present in the vascular endothelium of the human and nonhuman primate endometrium. , 2001, The Journal of clinical endocrinology and metabolism.

[10]  P. Chambon,et al.  Estradiol Accelerates Reendothelialization in Mouse Carotid Artery Through Estrogen Receptor-α but Not Estrogen Receptor-β , 2001 .

[11]  P. Hilton,et al.  Oestrogen and progesterone receptor expression in the female lower urinary tract, with reference to oestrogen status , 2000, BJU international.

[12]  J. Gustafsson,et al.  Differential expression of estrogen receptors α and β in adult rat accessory sex glands and lower urinary tract , 2000, Molecular and Cellular Endocrinology.

[13]  G. Fricchione,et al.  Cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia. , 2000, Circulation.

[14]  A. Taylor,et al.  Immunolocalisation of oestrogen receptor beta in human tissues. , 2000, Journal of molecular endocrinology.

[15]  J. Gustafsson,et al.  Cellular distribution of estrogen receptor β in neonatal rat bone , 2000 .

[16]  L. Sahlin,et al.  A Comparative Study of Estrogen Receptors α and β in the Rat Uterus , 1999 .

[17]  E. Balslev,et al.  Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia. , 1999, Scandinavian journal of urology and nephrology.

[18]  J. Gustafsson,et al.  Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors α and β , 1999 .

[19]  L. Doncarlos,et al.  Regulation of androgen receptor messenger ribonucleic acid expression in the developing rat forebrain. , 1999, Endocrinology.

[20]  R. Karas,et al.  Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. , 1999, The Journal of clinical investigation.

[21]  D. Edwards,et al.  Progesterone Regulates Proliferation of Endothelial Cells* , 1999, The Journal of Biological Chemistry.

[22]  J. Gustafsson,et al.  Increased expression of estrogen receptor-beta mRNA in male blood vessels after vascular injury. , 1998, Circulation research.

[23]  S. Ergün,et al.  Estrogen and progesterone receptors and estrogen receptor‐related antigen (ER‐D5) in human epididymis , 1997, Molecular reproduction and development.

[24]  R. Karas,et al.  Estrogen inhibits the vascular injury response in estrogen receptor α-deficient mice , 1997, Nature Medicine.

[25]  P. Rogers,et al.  Endometrial vascular smooth muscle oestrogen and progesterone receptor distribution in women with and without menorrhagia. , 1996, Human reproduction.

[26]  R. Karas,et al.  Human vascular smooth muscle cells contain functional estrogen receptor. , 1994, Circulation.

[27]  E. Barrack,et al.  Sexually dimorphic expression of estrogen receptors, but not of androgen receptors in human fetal external genitalia. , 1993, The Journal of clinical endocrinology and metabolism.

[28]  N. Sadick,et al.  A study of estrogen and progesterone receptors in spider telangiectasias of the lower extremities. , 1990, The Journal of dermatologic surgery and oncology.

[29]  C. Sjögren,et al.  Effect of oestrogen and progesterone on the blood flow in the lower urinary tract of the rabbit. , 1985, Acta physiologica Scandinavica.

[30]  M. Jenner,et al.  Hormonal Changes in Puberty: IV. Plasma Estradiol, LH, and FSH in Prepubertal Children, Pubertal Females, and in Precocious Puberty, Premature Thelarche, Hypogonadism, and in a Child with a Feminizing Ovarian Tumor , 1972 .

[31]  G. Celoria,et al.  [Study of testicular estrogenic production in normal individuals and in patients with various alterations of the seminiferous tube]. , 1965, Revista iberica de endocrinologia.

[32]  C. Foster Evaluation of seven oestrogen receptor beta antibodies for immunohistochemistry, western blotting, and flow cytometry in human breast tissue , 2003 .

[33]  M. Evans,et al.  Estrogen receptors alpha and beta have similar activities in multiple endothelial cell pathways. , 2002, Endocrinology.

[34]  A. Kitabatake,et al.  Evidence for a potential role of estrogen in the penis: detection of estrogen receptor-alpha and -beta messenger ribonucleic acid and protein. , 2002, Endocrinology.

[35]  J. Gustafsson,et al.  Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract. , 2000, Molecular and cellular endocrinology.

[36]  J. Gustafsson,et al.  Cellular distribution of estrogen receptor beta in neonatal rat bone. , 2000, Bone.

[37]  L. Sahlin,et al.  A comparative study of estrogen receptors alpha and beta in the rat uterus. , 1999, Biology of reproduction.

[38]  J. Gustafsson,et al.  Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J. Gustafsson,et al.  Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. , 1997, Endocrinology.