| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the * Department of Obstetrics and
Gynecology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong
Kong, SAR China; the Department of Obstetrics
and Gynecology, North Shore University Hospital, New York University Medical
College, Manhasset, New York; and the
Department of Urology, Medical College of
Wisconsin, Milwaukee, Wisconsin.
| Correspondence to: Dr Yibing Han, Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, China (e-mail: ybhan{at}cuhk.edu.hk). |
| Received for publication March 3, 2008; accepted for publication September 4, 2008. |
 |
Abstract |
|---|
 Top Abstract Materials and MethodsResultsDiscussionReferences |
|---|
(ER) in the testes of men with obstructive azoospermia (OA), maturation
arrest (MA), and Sertoli cell–only (SCO) histology. Testicular biopsies
were obtained from 10 patients with OA, 10 patients with MA (either early or
late arrest), and 8 patients with SCO who did not have hormonal abnormalities
and varicoceles. Expression of PR and ER was detected by
immunofluorescence and Western blot. PR was expressed in the spermatogenic,
Leydig, and Sertoli cells in the testes of OA patients. In the MA and SCO
patients, the expression of PR was reduced in all cell types as compared with
that in the OA patients. Western blot demonstrated that both the full-size
(120 KDa) and the truncated (52 KDa) isoforms of the PR were expressed in the
OA and MA testes. However, in the SCO testes, only the truncated isoform of PR
(52 KDa) was expressed. ER (66 KDa) was expressed principally in the
spermatogenic and Leydig cells in the OA testes. By immunohistochemistry
staining, expression of ER was decreased in the spermatogenic and
Leydig cells of the MA testes, whereas its expression was enhanced in the
Leydig cells of the SCO testes. However, by Western blot, expression of
ER was significantly reduced in the SCO testes as compared with that in
the OA and MA testes. We conclude that PR and ER may play a role in the
pathogenesis of the MA and SCO phenotype in patients with infertility.
Key words: Estrogen receptor , male infertility
The classic PR-A (90 KDa) and PR-B (120 KDa) and the membrane-bound PR (55
KDa) have all been detected in the human testes previously
(Shah et al, 2005). The
stage-specific expression of PR is most restricted to the spermatogenic cells
and Sertoli cells in the testis (Shah et
al, 2005). The mice null for steroidal receptor coactivator-1
(SRC-1; an intracellular PR coactivator) show reduced testicular growth and
fertility as compared with wild-type littermates
(Xu et al, 1998). Two kinds of
ER (ER and ERβ) have been discovered so far in the human male
reproductive tract. ERβ locates mainly in somatic cells and/or primary
spermatocytes. Its polymorphism is associated with male infertility (Aschim et
al, 2004,
2005). In contrast, ER
mainly locates in the efferent ductule epithelium and also in the Sertoli and
Leydig cells in human testes (Pelletier
and El-alfy, 2000; Taylor and
Al-Azzawi, 2000; Makinen et
al, 2001). However, some studies show no ER expression in
human testes (Makinen et al,
2001). Two ER isoforms (66 and 46 KDa) have been
demonstrated in rat testes and human immature germ cells
(Lambard et al, 2004;
Staub et al, 2005).
Importantly, the polymorphism of ER is associated with elevated plasma
levels of follicle-stimulating hormone (FSH) and idiopathic azoospermia in
humans (Suzuki et al, 2002).
The commonly accepted role of ER is to reabsorb the fluid of the
seminiferous tubules just before the spermatozoa enter into the epididymis,
which might concern the function of aquaporins
(Picciarelli-Lima et al,
2006).
It is still unknown whether there are any differences in the expression of
PR and ER between normal and infertile human testes. The objective of
this study is to determine the expression of PR and ER in the testes of
men with infertility, and the possible relationship with the pathogenesis of
this condition. It is the first report of abnormal expression of both PR and
ER in the testes of infertile men.
|
Materials and Methods |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Indirect Immunofluorescence Techniques
The primary antibodies for PR and ER were polyclonal rabbit
anti-human PR IgG (Cat SC-539; Santa Cruz Biotech, Santa Cruz, California),
which was formed against the internal region, and polyclonal mouse anti-human
ER IgG (Cat SC-8002; Santa Cruz Biotech), which was against the C
terminus. Tissue specimens were incubated with the primary PR and ER
antibodies at a 1:100 dilution overnight at room temperature. All incubations
were carried out in a humidified chamber. Sections were rinsed 5 times with
diluent and incubated for approximately 45–60 minutes with 1:50 dilution
of fluorescein-conjugated affinity-purified goat antiserum to rabbit IgG
(Santa Cruz Biotech). The sections were then washed 5 times with diluent and
viewed by epifluorescence with a Zeiss IM 35 microscope (Oberkochen, Germany).
Tissue sections incubated with either buffer, normal serum (normal rabbit
serum; Sigma, St Louis, Missouri), or the secondary conjugated antibody
without primary antibody were utilized as negative controls. Staining was
considered positive if the tissue demonstrated immunofluorescence staining,
and was graded on a relative scale of no staining, weak staining, and
prominent staining.
Western Blot Analysis
Tissue specimens were homogenized in Tris-HCl with 1 mM serine protease
inhibitor PMSF. The homogenates were centrifuged at 11 950 x g
for 10 minutes to remove cellular debris. Proteins were extracted with 1%
sodium dodecyl sulfate (SDS) for 2 hours at 4°C. Protein concentrations of
the extracts were determined from the absorbency at 260 and 280 nm by
spectrophotometer. Aliquots (30–50 µg) of the protein extracts were
separated by electrophoresis on a 12% SDS–polyacrylamide gel
electrophoresis gel, transferred to nitrocellulose paper, and blocked with 5%
milk powder in TBS buffer (10 mM/L Tris-HCl, pH 8.0, 150 mM/L NaCl) for 1 hour
at room temperature. The blots were washed in TBST (TBS containing 0.05%
Tween-20) and then incubated overnight with PR and ER polyclonal
antibody diluted to 1:400 with phosphate-buffered saline containing 2.5%
bovine serum albumin. The blots were then washed in TBST, incubated for 1 hour
with horseradish peroxidase–conjugated anti-rabbit immunoglobulins
(Cappel, Durham, North Carolina) diluted to 1:10 000 in TBST and followed by
enhanced chemiluminescence (Amersham Life Science, Arlington Heights,
Illinois) staining. This experiment was repeated 3 times using separate
samples.
|
Results |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
|
|
ER studies
ER was strongly localized in the nuclei of the spermatogenic cells
and the cytoplasm of the Leydig cells in the OA testes
(Figure 3A), and was weakly
expressed in the MA testes (Figure
3B). In the SCO testes, expression in Leydig cells was
significantly increased, whereas the Sertoli cells were negative for ER
staining (Figure 3C). Negative
controls exhibited no staining in each case
(Figure 3D). Western blot data
demonstrated that both OA and MA testes had high expression of ER at 66
kDa (Figure 2B, lanes NL and
MA); however, the expression in SCO testes was dramatically reduced
(Figure 2B, lane S).
|
|
Discussion |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Expressed in Human Testes, mPRβ, and mPR
). PR-A and PR-B are translated from the
same gene; however, their transcription is initiated at different promoters.
The PR-A isoform differs from the PR-B isoform in lacking the first 164 amino
acids contained in PR-B (Hanekamp et al,
2003). PR-C is smaller than the other 2 isoforms, truncated at the
N-terminal domain, and known to have unique transcriptional potentiating
properties (Wei et al, 1997).
Other alternative transcriptions of PR gene generate the other isoforms of PR,
such as PR-S and PR-T. Multiple PR mRNA transcripts have been shown to exist
in a variety of human tissues, which give rise to several molecular weights
(eg, 120, 90, 76–82, and 60–64 KDa;
Gadkar-Sable et al, 2005). It
has been found that both the genomic (90 and 120 KDa) and the membrane-bound
PRs (55 and 29 KDa) exist in the human testes
(Sauber et al, 1996; Luconi et
al, 1998,
2004;
Losel et al, 2005;
Shah et al, 2005). As a
regulator of reproductive events, progesterone has been detected at high
levels in the testicular tissue (Leinonen
et al, 1980; Gadkar-Sable et
al, 2005). Following binding to its intracellular and membrane
receptor, progesterone begins to act in both a genomic mode and a nongenomic
mode.
In this study, 2 isoforms of PR (120 and 52 KDa) are identified in human testes, which might be the classic and the nonclassic membrane-bound respectively. Expression of the 120-KDa isoform of PR is absent in the testes of SCO patients, and the expression of the 52-KDa isoform of PR is decreased in the SCO and MA testes according to the Western blot (Figure 2A). This may indicate that: 1) Expression of the 52-KDa isoform of PR in the OA testes is significantly higher than that in the MA and SCO testes. Thus, the 52-KDa isoform of PR might be independently transcribed upon the full-length isoform. 2) Expression of PR in the Sertoli cells is decreased in the MA testes and almost no PR is detected in the SCO testes. So, in contrast to the expression of PR mRNA, which is restricted to the spermatogenic and Sertoli cells as previously indicated, we postulate that the expression of the 120-KDa isoform of PR is mostly restricted to the spermatogenic cells (Shah et al, 2005). 3) Expression of PR in the Leydig cells is enhanced in the SCO testes. Because the expression of PR mRNA is only occasionally detected in the Leydig cells in normal human testes, we hypothesize that the increased expression of PR in the Leydig cells of the SCO patients might indicate a different type of PR or a potentially different control system for PR in the spermatogenic cells and in the Leydig cells (Shah et al, 2005). This is consistent with the conclusion that the PR (45–57 KDa) expressed in the murine Leydig cell line is the nonclassic type (El-Hefnaway et al, 2000). In this study, we found that the PR is expressed in the cytoplasm of the spermatogenic and Sertoli cells and the nuclei of the Leydig cells. Furthermore, the expression of the 52-KDa PR in the Leydig cells is significantly increased in the SCO testes based upon histological staining (Figure 1). We conclude that the absence of the classic type of PR in the spermatogenic cells might be involved in the spermatogenic failure seen in the MA and SCO testes. The absence of the classic PR in the spermatogenic cells might stimulate the expression of the nonclassic PR in the Leydig cells possibly through a negative feedback mechanism.
Two forms of ER (ER and ERβ) have been discovered so far.
Expression of ERβ is more ubiquitous than that of ER
(Taylor and Al-Azzawi, 2000).
Expression sites of ER in the testes are controversial. Some authors
have detected ER in the nuclei of the Leydig cells in humans, whereas
others indicate that ER is expressed in the Sertoli, Leydig, and
peritubular myoid cells in the rat and is restricted to the Leydig cells in
the fetal testes (Pelletier and El-alfy,
2000; Makinen et al,
2001; O'Donnell et al,
2001; Lucas et al,
2008). Two isoforms of ER (66 and 46 KDa) have been found
in the human and primate testes because of alternative splicing of the
C-terminal region (Saunders et al,
2002; Hirata et al,
2003; Staub et al,
2005). The nonclassic ER (67 KDa) is expressed in human
ejaculated spermatozoa and directly interacts with the
phosphatidylinositol-3-OH kinase pathway. Variant types of ER (66 and
46 KDa) have been detected in human spermatogenic cells, whereas only the
66-KDa isoform of ER is detected in human mature spermatozoa
(Lambard et al, 2004). In this
study, only the 66-KDa ER expressed in the nuclei of the spermatogenic
cells and the cytoplasm of the Leydig cells is detected. Expression of
ER in the spermatogenic cells decreases in the MA testes by
immunofluorescence staining, whereas the expression is similar to Western blot
(Figures 2B and
3). The Sertoli cells are
negative for ER. We found that although the expression of ER is
enhanced in the Leydig cells in the SCO testes, its expression in the whole
testes is dramatically decreased as indicated by Western blot. We conclude
that: 1) expression of ER in the spermatogenic cells might be important
for normal spermatogenesis; 2) the patterns of expression in the spermatogenic
cells (nucleus pattern) and the Leydig cells (cytoplasm pattern) might
indicate that different types of ER exist in the 2 cell types, though
only 1 isoform (66 KDa) is discovered here in human testes.
Functional Analysis of the PR/ER Expressed in Human Testes
Direct functions of progesterone in testes include steroidogenesis, Sertoli
cell function, and spermatogenesis (Walton
et al, 2006). Progesterone and its analogues (including 17,
20β-dihydroxy-4-pregnen-3-one and 17,
20-dihydroxy-4-pregnen-3-one) are reported to induce hyperactive
motility, acrosomal reaction, spermatogonial DNA synthesis, and spermatogenic
meiosis in mammals, fish, and amphibians
(Calogero et al, 2000;
Losel and Wehling, 2003;
Losel et al, 2003;
Miura et al, 2006).
Furthermore, the expression of PR on the spermatozoa has been shown to be
related to sperm fertilizing capability in humans
(Fukui et al, 2000). However,
in contrast to adult female mice with disrupted classic PR, which display
significant defects in reproductive functions, adult male mice with disrupted
classic PR show no impairment of fertility
(Dube and Tremblay, 1979;
Heikinheimo et al, 1995;
Lydon et al, 1995).
Being produced within the testes by the aromatization of testosterone,
estrogen disrupts the development of fetal Leydig cells, inhibits testosterone
production in the Leydig cells, stimulates gonocyte and spermatogonia
proliferation, and enhances spermatogenesis by inhibiting apoptosis of the
postmeiotic spermatogenic cells (Kular,
1988; Li et al,
1997; Miura et al,
1999). Estradiol has been confirmed to exert stimulatory effects
on premitotic DNA synthesis in the stage I segment of the seminiferous
epithelium in vitro and to function directly on neonatal rat testicular
gonocytes by the PDGF or HSp90 pathways
(Thuillier et al, 2003;
Wang et al, 2004;
Wahlgren et al, 2008). The
inhibitory effects of estrogens on testicular steroidogenesis are mediated
exclusively via ER (Cederroth et al,
2007). As a result, in ER–/– mice,
plasma/testicular testosterone concentrations, spermatogenesis,
steroidogenesis, and fertility are influenced
(Walker and Korach 2004;
Gould et al, 2007). In
ER–/– mice, Leydig cell volumes are decreased
and a significant loss of all kinds of spermatogenic cells through active
caspase-3 activation and infertility occurs
(Gould et al, 2007). However,
the spermatogenic cells of ER–/– mice have
normal functions after transplantation to wild-type mouse testes
(Mahato et al, 2000). Estrogen
also affects Sertoli cell proliferation and may suppress differentiation, but
no changes were observed on the number of Sertoli cells and spermatogonia in
the ER–/– mouse. So, the function of ER
on germ cells remains questionable as revealed in this mouse model. Similarly,
in human patients with abnormalities of ER and aromatase genes, high
levels of testosterone, luteinizing hormone (LH), and FSH are displayed. These
men also have low sperm viability, number, and motility; azoospermia; and
sometimes cryptorchidism (Smith et al,
1994; Herrmann et al, 2002;
Suzuki et al, 2002;
Maffei et al, 2004;
Guarducci et al, 2006).
In this study, testicular tissue from OA and nonobstructive azoospermia
(NOA) patients, including MA and SCO, is used. MA is characterized by the
presence of germ cells that do not complete spermatogenic development, as seen
on testicular biopsy. SCO is characterized by the presence of no germ cells
but only Sertoli cells as seen on testicular biopsy. Both groups of NOA
patients in this study did not show an increase in serum FSH. However, it is
unclear whether progesterone, estrogen, and/or testosterone changes in these
patients. Disruption of PR and ER in the testes might cause the steroid
hormones mentioned above to change accordingly. It has been demonstrated that
progesterone stimulates testosterone synthesis in the rat testes by regulating
the steroid acute regulatory gene (StAR;
Schwarzenbach et al, 2003).
And increased testosterone, LH, and FSH synthesis might also occur as a result
of ER mutations via the negative effect on the inhibition of testicular
steroidogenesis (Cederroth et al,
2007). Therefore, the combined decrease of PR and ER might
be one of the major causes for the infertility of the MA and SCO patients.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Aschim EL, Saether T, Eiger R, Grotmol T, Haugen TB. Differential distribution of splice variants of estrogen receptor beta in human testicular cells suggests specific functions in spermatogenesis. J Steroid Biochem Mol Biol. 2004;92: 97 –106.[CrossRef][Medline]
Calogero A, Burrello N, Barone N, Palermo I, Grasso U, D'Agata R.
Effects of progesterone on sperm function: mechanism of action. Hum
Reprod. 2000;15: 28
–45.
Cederroth CR, Schaad O, Descombes P, Chambon P, Vassalli JD, Nef S.
ER is a major contributor to estrogen-mediated fetal testes dysgenesis
and cryptorchidism. Endocrinology. 2007; 148: 5507
–5519.
Dube JY, Tremblay RR. Search for progesterone receptors in testes from various animal species. Mol Cell Endocrinol. 1979; 16: 39 –44.[CrossRef][Medline]
El-Hefnaway T, Manna PR, Luconi M, Baldi E, Slotte JP, Huhtaniemi
I. Progesterone action in a murine Leydig tumor cell line (mLTC-1), possibly
through a nonclassical receptor type. Endocrinology. 2000; 141: 247
–255.
Fukui K, Hori R, Yoshimoto I, Ochi H, Ito M. Correlation between progesterone binding sites on human spermatozoa and in vitro fertilization outcome. Gynecol Obstet Invest. 2000; 49: 1 –5.[CrossRef][Medline]
Gadkar-Sable S, Shah C, Rosario G, Sachdeva G, Puri C. Progesterone receptors: various forms and functions in reproductive tissues. Front Biosci. 2005; 10: 2118 –2130.[Medline]
Gould ML, Hurst PR, Nicholson HD. The effects of oestrogen
receptors and β on testicular cell number and steroidogenesis in
mice. Reproduction. 2007; 134: 271
–279.
Guarducci E, Nuti F, Becherini L, Rotondi M, Balercia G, Forti G,
Krausz C. Estrogen receptor promoter polymorphism: stronger estrogen
action is coupled with lower sperm count. Hum Reprod. 2006; 21: 994
–1001.
Hanekamp EE, Gielen SC, Can Oosterhoud SA, Burger CW, Grootegoed JA, Huikeshoven FJ, Blok LJ. Progesterone receptors in endometrial cancer invasion and metastasis: development of a mouse model. Steroids. 2003;68: 795 –800.[CrossRef][Medline]
Heikinheimo O, Mahony MC, Gordon K, Hsiu JG, Hodgen GD, Biggons WE. Estrogen and progesterone receptor mRNA are expressed in distinct pattern in male primate reproductive organs. J Assist Reprod Genet. 1995;12: 198 –204.[CrossRef][Medline]
Hermann BL, Saller B, Janssen OE, Gocke P, Bochisch A, Sperling H,
Mann K, Broecker M. Impact of estrogen replacement therapy in a male with
congenital aromatase deficiency caused by a novel mutation in the CYP19 gene.
J Clin Endocrinol Metab. 2002; 87: 5476
–5484.
Hess RA, Carnes K. The role of estrogen in testis and the male reproductive tract: a review and species comparison. Anim Reprod. 2004;1: 5 –30.
Hirata S, Shoda T, Kato J, Hoshi K. Isoform/variant mRNAs for sex steroid hormone receptors in humans. Trends Endocrinol Metab. 2003;14: 124 –129.[CrossRef][Medline]
Kular K. Induction of precocious maturation of spermatogenesis in
infant rats by human menopausal gonadotropin and inhibition by simultaneous
administration of gonadotropins and testosterone.
Endocrinology. 1988; 122: 34
–39.
Lambard S, Galeraud-Denis I, Saunders PTK, Carreau S. Human immature germ cells and ejaculated spermatozoa contain aromatase and oestrogen receptors. J Mol Endocrinol. 2004; 32: 279 –289.[Abstract]
Leinonen P, Hammond G, Vikho R. Testosterone and some of its
precursors and metabolites in the human epididymis. J Clin
Endocrinol Metab. 1980;51: 423
–428.
Li H, Papadopoulos V, Vidic B, Dym M, Culty M. Regulation of rat
testis gonocyte proliferation by platelet-derived growth factor and estradiol:
identification of signaling mechanisms involved.
Endocrinology. 1997; 138: 1289
–1298.
Losel R, Breiter S, Seyfert M, Wehling M, Falkenstein E. Classic and non-classic progesterone receptors are both expressed in human spermatozoa. Horm Metab Res. 2005; 37: 10 –14.[CrossRef][Medline]
Losel R, Falkenstein E, Feruing M, Schultz A, Tilllmann HC,
Rossol-Haseroth K, Wehling M. Nongenomic steroid action: controversies,
questions, and answers. Physiol Rev. 2003; 83: 965
–1016.
Losel R, Wehling M. Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol. 2003; 4: 46 –56.[CrossRef][Medline]
Lucas TFG, Siu ER, Esteves CA, Monteiro HP, Oliveira CA, Porto CS,
Lazari MFM. 17beta-estradiol induces the translocation of the estrogen
receptors ESR1 and ESR2 to the cell membrane, MAPK 3/1 phosphorylation and
proliferation of cultured immature rat Sertoli cells. Biol
Reprod. 2008;78: 101
–114.
Luconi M, Bonaccorsi L, Maggi M, Pecchioli P, Krausz C, Forti G,
Baldi E. Identification and characterization of functional nongenomic
progesterone receptors on human sperm membrane. J Clin Endocrinol
Metab. 1998;83: 877
–885.
Luconi M, Francavilla F, Porazzi I, Macerola B, Forti G, Baldi E. Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids. 2004;69: 553 –559.[CrossRef][Medline]
Lydon PJ, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CAJr,
Shyamala G, Conneely OM, O'Mallery BE. Mice lacking progesterone receptor
exhibit pleiotropic reproductive abnormalities. Genes
Dev. 1995;9: 2266
–2278.
Maffei L, Murata Y, Rochira C, Tubert G, Aranda C, Vazquez M, Clyne
CD, Davis S, Simpson ER, Carani C. Dysmetabolic syndrome in a man with a novel
mutation of the aromatase gene: effects of testosterone, alendronate, and
estradiol treatment. J Clin Endocrinol Metab. 2004; 89: 61
–70.
Mahato D, Goulding EH, Korach KS, Eddy EM. Spermatogenic cells do
not require estrogen receptor-alpha for development or function.
Endocrinology. 2000; 141: 1273
–1276.
Makinen S, Makela S, Zhang W, Warner M, Rosenlund B, Salmi S,
Hovatta O, Gustafsson J. Localization of oestrogen receptors alpha and beta in
human testis. Mol Hum Reprod. 2001; 7: 497
–503.
Miura T, Higuchi M, Ozaki Y, Ohta T, Miura C. Progestin is an
essential factor for the initiation of the meiosis in spermatogenetic cells of
the eel. Proc Natl Acad Sci U S A. 2006; 103: 7333
–7338.
Miura T, Miura C, Ohta T, Nader MR, Todo T, Yamauchi K. Estradiol-17β stimulates the renewal of spermatogonial stem cells in males. Biochem Biophys Res Commun. 1999; 264: 230 –234.[CrossRef][Medline]
O'Donnell L, Robertson KM, Jones ME, Simpson ER. Estrogen and
spermatogenesis. Endocr Rev. 2001; 22: 289
–318.
Oettel M, Mukhopadhyay AK. Progesterone: the forgotten hormone in men? Aging Male. 2004; 7: 236 –257.[CrossRef][Medline]
Pelletier G, El-alfy M. Immunocytochemical localization of estrogen
receptors and β in the human reproductive organs. J
Clin Endocrinol Metab. 2000; 85: 4835
–4840.
Picciarelli-Lima P, Oliverira AG, Reis AM, Kalapothakis E, Mahecha GAB, Hess RA, Oliverira CA. Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects, in modulating the aquaporin-9 expression in the rat efferent ductules. Reprod Biol Endocrinol. 2006; 4: 51 –60.[CrossRef][Medline]
Revelli A, Massobrio M, Tesarik J. Nongenomic actions of steroid
hormones in reproductive tissues. Endocr Rev. 1998; 19: 3
–17.
Sauber K, Edwards DP, Meizel S. Human sperm plasma membrane progesterone receptor(s) and the acrosome reaction. Biol Reprod. 1996;54: 993 –1001.[Abstract]
Saunders PTK, Millar MR, Macpherson S, Irvine DS, Groome NP, Evans
LR, Sharpe RM, Scobie GA. ER β1 and the ER β2 splice variant are
expressed in distinct cell populations in the adult human testis. J
Clin Endocrinol Metab. 2002; 87: 2706
–2715.
Schwarzenbach H, Manna PR, Stocco DM, Chakrabarti G, Mukhopadhyay
AK. Stimulatory effect of progesterone on the expression of steroidogenic
acute regulatory protein in MA-10 Leydig cells. Biol
Reprod. 2003;68: 1054
–1063.
Shah C, Modi D, Sachdeva G, Gadkar S, Puri C. Coexistence of
intracellular and membrane-bound progesterone receptors in human testis.
J Clin Endocrinol Metab. 2005; 90: 474
–483.
Smith EP, Boyd J, Trank GR, Takahashi H, Cohen RM, Specker B,
Eilliams TC, Lubahn DB, Korach KS. Estrogen resistance caused by a mutation in
the estrogen-receptor gene in a man. N Engl J Med. 1994; 331: 1056
–1061.
Staub C, Rauch M, Ferriere F, Trepos M, Dorval-Coiffec I, Saunders
PT, Cobellis G, Flouriot G, Saligaunt C, Jegou B. Expression of estrogen
receptor ESR1 and its 46-Kda variant in the gubernaculums testis.
Biol Reprod. 2005; 73: 703
–712.
Suzuki Y, Sasagawa I, Itoh K, Ashida J, Muroya K, Ogata T. Estrogen receptor alpha gene polymorphism is associated with idiopathic azoospermia. Fertil Steril. 2002; 78: 1341 –1343.[CrossRef][Medline]
Taylor AH, Al-Azzawi F. Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol. 2000; 24: 145 –155.[Abstract]
Thuillier E, Wang Y, Culty M. Prenatal exposure to estrogenic
compounds alters the expression pattern of platelet-derived growth factor
receptors and β in neonatal rat testis: identification of
gonocytes as targets of estrogen exposure. Biol
Reprod. 2003;68: 867
–880.
Wahlgren A, Svechnikov K, Strand ML, Jahnukainen K, Parvinen M,
Gustafsson JA, Soder O. Estrogen receptor β selective ligand
5-androstane-3β, 17 β-Diol stimulates spermatogonial
deoxyribonucleic acid synthesis in rat seminiferous epithelium in vitro.
Endocrinology. 2008; 149: 2917
–2922.
Walker VR, Korach KS. Estrogen receptor knockout mice as a model for endocrine research. ILAR J. 2004; 45: 455 –461.[Medline]
Walton MJ, Bayne RAJ, Wallace I, Baird DT, Anderson RA. Direct
effect of progesterone on gene expression in the testis during gonadotropin
withdrawal and early suppression of spermatogenesis. J Clin
Endocrinol Metab. 2006;91: 2526
–2533.
Wang Y, Thuillier R, Culty M. Prenatal estrogen exposure
differentially affects estrogen receptor-associated proteins in rat testis
gonocytes. Biol Reprod. 2004; 71: 1652
–1664.
Wei L, Norris LBM, Baker CJ. An N-terminally truncated third progesterone receptor protein, PR-C, forms heterodimers with PR(B) but interferes in PR(B)-DNA binding. J Steroid Mol Biol. 1997; 62: 287 –297.[CrossRef]
Xu J, Qiu Y, Demayo J, Tsai SY, Tsai MY, O'Malley BW. Partial
hormone resistance in mice with disruption of the steroidal receptor
coactivator-1 (SRC-1) gene. Science. 1998; 279: 1922
–1925.
This article has been cited by other articles:
|
|
 |
|
  Q. Zhang, Q. Bai, Y. Yuan, P. Liu, and J. Qiao Assessment of Seminal Estradiol and Testosterone Levels as Predictors of Human Spermatogenesis J Androl, March 1, 2010; 31(2): 215 - 220. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
