Nuclear location of hormone-free estrogen receptors by monoclonal antibodies could be a tissue-fixation dependent artifact

The 'two-step' model proposed by Jensen and his collaborators for explaining estrogen action conceptualized hormone-free estrogen receptors (ER) to be cytoplasmic, and hormone-filled, transformed ER to be nuclear. Applying monoclonal antibodies which recognized epitopes in ER and formaldehyde-fixed tissues, King et al demonstrated exclusively nuclear staining in target tissues utilizing immunoperoxidase technique. Recently these antibodies have become commercially available enabling other investigators to conduct studies. In this report, using these monoclonal antibodies we have demonstrated that a change in the concentration of formaldehyde alters the staining pattern yielding cytoplasmic instead of nuclear staining in calf uterus, MCF-7 cells, and ER(+) human breast cancer. In addition, neutralization of the antibody activity was not achieved with freshly prepared ER(+) cytosols. Formaldehyde-treated cytosols were essential. These results ought to caution investigators in determining in vivo location of antigens based on the staining pattern obtained in fixed tissues. Furthermore, this effect of formaldehyde on estrogen receptors may be applicable to other steroid hormone receptors.     

Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goals of this study were to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERα), and assess cells expressing both AR and ERα, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERα. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERα expression was increased in BPH epithelium. However, stromal ERα expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR and ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR and ERα) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH.     

The presence of a hitherto undefined high-capacity androgen binding macromolecule in human ovarian cancer tissue

Sex hormone binding globulin (SHBG) is known to interfere in the quantitation of androgen receptors (AR) if dihydrotestosterone (DHT) is used. We used a monoclonal antibody to remove SHBG from cytosol. In cytosol of benign prostatic hyperplastic (BPH) tissue low capacity binding for DHT, but not for R1881, was found after removal of SHBG. AR were detected in 18 of 20 ovarian cancer cytosols. In the two AR-negative cases, non-saturable binding for DHT, testosterone and R1881 was observed. Incubation with anti-SHBG did not change this. An hitherto undefined androgen binding macromolecule(s), with high-capacity binding for natural and synthetic androgens, but not for estrogen and progesterone, seems to be present in these ovarian cancer tissues. The functionality of these androgen binding macromolecules in ovarian cancer is yet to be demonstrated.     

Cell-specific distributions of estrogen receptor alpha (ERα) and androgen receptor (AR) in anterior pituitary glands from adult cockerels as revealed by immunohistochemistry

Estrogens and androgens play important roles in regulating the hormone-secreting functions of the pituitary gland by binding to their corresponding receptors. However, the expression of estrogen receptors (ERs) and the androgen receptor (AR) and the cell types containing ERs and AR in the anterior pituitary gland of adult chickens have not been well-studied. In this study, the distribution of ERα, AR and their corresponding cell types in the anterior pituitary gland of adult cockerels was detected by immunohistochemistry. The results showed that ERα was expressed in 68.63 % of luteinizing hormone (LH) producing cells but was not found in thyrotropes, lactotropes, somatotropes, corticotropes and folliculo-stellate (FS) cells. Pituitary hormone and AR double labeling results showed that about 37 % of LH cells and 50 % of thyroid-stimulating hormone (TSH) producing cells expressed AR, respectively. In contrast, less than 1 % of the somatotropes had an AR positive signal and AR signals were not detected in lactotropes, corticotropes or FS cells. In addition, there were only a few AR and ERα dual-labeled cells observed. These novel results provide evidence for a cell-specific distribution of ERα and AR in the anterior pituitary from adult cockerels by immunohistochemistry. The different distributions of ERα and AR in the LH cells suggest that the feedback-regulating mechanisms of estrogen and androgen on the pituitary hormones secretion are different. The functions and related mechanisms still need to be elucidated further.     

A comparison of estrogen and androgen receptor levels in human prostatic tissue from patients with non-metastatic and metastatic carcinoma and benign prostatic hyperplasia

Estrogen receptors (ER, N = 72) and androgen receptors (AR, N = 33) were determined by high pressure liquid chromatography (HPLC) in 72 human prostatic tissues obtained at prostatectomy, and exploratory statistical analyses of the resulting data were performed. To facilitate use of these data as well as other pertinent information from the patient charts, a program for a comparatively large data base was implemented on a Wang minicomputer. The median values of cytosolic AR in the four cancer stages examined were statistically different from each other (P = 0.01), with AR increasing from stages A through D. Even though ER differences between the four stages were not significant (P = 0.13), there was a trend, in the data examined, for median ER values to decrease with stages B through D. On the other hand, median BPH values for both ER and AR were found to lie mid-scale compared with the respective cancer stages, leading to the conclusion that receptor measurements probably cannot distinguish between CA and BPH in human prostatic tissue, at least as measured by competitive binding techniques.     

Androgen receptors in rat and human prostate

In intact adult rats almost all androgen receptor (AR) sites of the rat ventral prostate (RVP) are occupied by endogenous dihydrotestosterone, and about 80% of these sites are nuclear. Nuclear AR disappears rapidly after castration (half-life of 3 h). The amount of cytosolic AR does not change within the initial 36 h, then markedly decreases during the next 2-5 days. An early and specific action of androgen is a remarkable increase of its own receptor. RVP also contains an estradiol receptor (ER) which rapidly disappears after castration and which, contrary to AR, is predominantly localized in the cytosol of stromal elements. The published procedures for steroid receptors grossly underestimate receptors concentrations in normal (NHP) and hyperplastic (BPH) human prostate. We have recently established a reliable method for the measurement of total AR, and we have found no difference in AR concentrations between NHP and BPH. BPH also contains a progesterone receptor and an elusive ER. Finally, we have used specific immunoglobulins in sex hormone binding plasma protein (SBP) for the demonstration of SBP-like immunoreactivity by the indirect immunofluorescence technique. The specific antigenic material was exclusively localized in the cytoplasm of BPH epithelial cells.     

人乳腺癌cAMP结合蛋白

建立了测定人乳腺癌胞浆ｃＡＭＰ结合蛋白（ｃＡＭＰｂ．ｐ．）方法。综合研究了其温度、保温时间、配体浓度、稳定性等条件。ｃＡＭＰｂ．ｐ．的Ｋ_Ｄ值为２．９０×１０~（－８）ｍｏｌ／Ｌ．并测定了６０例雌激素受体（ＥＲ）Ｆｕ性乳腺癌标本的ｃＡＭＰｂ．ｐ．含量。此组病人术后均接受系统的内分泌治疗,ＥＲ／ｃＡＭＰｂｐ,比值范围为７．７～３６２×１０~（－３）,ＥＲ／ｃＡＭＰｂ．ｐ．比值≥４０×１０~（－３）的五年生存率明显高于比值＜４０×１０~（－３）组,（ｐ＜０．００５）．表明测定ＥＲ／ｃＡＭＰｂ．ｐ．比值对预测患者内分泌治疗疗效,优于单独测定ＥＲ．     

Expression of hormone receptors predicts survival and platinum sensitivity of high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSOC) has abundant expression of hormone receptors, including androgen receptor (AR), estrogen receptor α (ER), and progesterone receptor (PR). The effects of hormone receptors on prognosis of HGSOC were first evaluated in online databases. Their prognostic values were then explored and validated in our inhouse TJ-cohort (92 HGSOC patients) and in a validation cohort (33 HGSOC patients), wherein hormone receptors were detected immunohistochemically. High expression of hormone receptors denoted longer progression-free survival (PFS), overall survival (OS), and platinum-free interval (PFI). Platinum-sensitive patients had higher expression of hormone receptors than their counterparts. Correlation analysis revealed significant positive correlations between hormone receptors expression and survival. AR, ER, and PR had predictive and prognostic values, alone and in combination. By receiver operating characteristic curve (ROC) analysis, co-expression of AR, ER, and PR had an improved predictive performance with an area under the curve (AUC) value of 0.945. Expression of hormone receptors predicts survival and platinum sensitivity of HGSOC. AR, ER, and PR might be feasible prognostic biomarkers for HGSOC by immunohistochemical analysis.     

Hormonal effects of tetrabromobisphenol A using a combination of in vitro and in vivo assays

The aim of this study was to investigate the hormonal effects of tetrabromobisphenol A (TBBPA) in vitro on recombinant yeasts and in vivo on mosquitofish (Gambusia affinis). The in vitro bioassays for (anti-)androgenic activities showed that TBBPA had a weak androgenic activity in vitro with recombinant yeast systems carrying human androgen receptor (hAR). In the in vivo bioassays, the gene expression patterns of vitellogenin (Vtg), estrogen receptors (ERα and ERβ), and androgen receptors (ARα and ARβ) in adult males and juveniles after exposure to TBBPA for 60 days were evaluated. Significant up-regulation of Vtg, ERα, and ERβ mRNAs was observed in the liver after exposure to 500 nM of TBBPA. In the testis, the lowest concentration of TBBPA (50 nM) markedly induced Vtg, ERβ, and ARβ mRNA expression, but the same concentration significantly inhibited ARα mRNA expression. In addition, in juveniles, 100 nM of TBBPA significantly up-regulated the expression of Vtg, ERβ, and ARα mRNAs. However, TBPPA did not cause histological alterations in the liver and testis of adult male mosquitofish. The results from this present study suggest that TBBPA could display low but multiple hormonal activities despite its low toxicity to mosquitofish.     

Immunolocalization of estrogen receptor alpha, estrogen receptor beta and androgen receptor in the pre-, peri- and post-pubertal stallion testis

In various species, androgens and estrogens regulate the function of testicular Leydig, Sertoli, peritubular myoid, and germ cells by binding to their respective receptors and eliciting a cellular response. Androgen receptor (AR) is expressed in Sertoli cells, peritubular myoid cells, Leydig cells and perivascular smooth muscle cells in the testis depending on the species, but its presence in germ cells remains controversial. Two different estrogen receptors have been identified, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), and their localization and function in testicular cells varies depending on the species, developmental stage of the cell and type of receptor. The localization of AR in an immature and mature stallion has been reported but estrogen receptors have only been reported for the mature stallion. In the present study, the localizations of AR and ERα/ERβ were investigated in pre-pubertal, peri-pubertal and post-pubertal stallions. Testes were collected by routine castration from 21 horses, of light horse breeds (3 months-27 years). Animals were divided into the following age groups: pre-pubertal (3-11 months; n=7), peri-pubertal (12-23 months; n=7) and post-pubertal (2-27 years; n=7). Testicular tissue samples were fixed and embedded, and the presence of AR, ERα and ERβ was investigated by immunohistochemistry (IHC) using procedures previously validated for the horse. Primary antibodies used were rabbit anti-human AR, mouse anti-human ERβ and rabbit anti-mouse ERα. Sections of each region were incubated with normal rabbit serum (NRS; AR and ERα) or mouse IgG (ERβ) instead of primary antibody to generate negative controls. Androgen receptors were localized in Leydig, Sertoli and peritubular myoid cells of all ages. Estrogen receptor alpha was localized in Leydig and germ cells of all ages but only in pre- and peri-pubertal Sertoli cells and post-pubertal peritubular myoid cells. Estrogen receptor beta was localized in Leydig and Sertoli cells of all ages but in only pre-pubertal germ cells and absent in peritubular myoid cells of all ages. Taken together, the data suggest that estrogen regulates steroidogenesis by acting through ERα and ERβ in the Leydig cells and promotes gametogenesis by acting through ERβ in the Sertoli cells and ERα in the germ cells. In contrast androgen receptors are not found in germ cells throughout development and thus are likely to support spermatogenesis by way of a paracrine/autocrine pathway via its receptors in Leydig, Sertoli and peritubular myoid cells.     

Arachidonic acid as a possible modulator of estrogen, progestin, androgen, and glucocorticoid receptors in the central and peripheral tissues

In an attempt to learn whether modulation of steroid hormone receptor by arachidonate is generalized or not, the arachidonate effect was examined in cytosol estrogen (ER), progestin (PR), androgen (AR) and glucocorticoid receptors (GCR) from the central and peripheral tissues of rats by sucrose density gradient centrifugation, and gel filtration on LH20 columns or dextran-coated charcoal absorption. Arachidonate and other long-chain fatty acids appear to inhibit the specific binding of estrogen ([3H]R2858), progestin ([3H]R5020), androgen ([3H]R1881) and glucocorticoid ([3H]dexamethasone) to the respective receptors in brain (neonatal cerebral cortex and hypothalamus-preoptic area, HPOA), uterus and prostate, with the exception of the potentiating effect on the brain estrogen receptors. The potency of the unsaturated fatty acids paralleled to some degree the number of cis double bonds and carbon, in that oleate (C18:1) arachidonate (C20:4) docosahexaenoate (C22:6). The arachidonate inhibition was dose-dependent in the tissue steroid hormone receptors, except for dose-dependent potentiation of the brain cortical estrogen receptors. Inhibitory potency as expressed by the concentration for 50% maximum inhibition (Ki) was in the range of 11-18 microM for the receptors other than the uterine estrogen receptors with the value of 44 microM, suggesting lower sensitivity for the estrogen receptor to the arachidonate effect in the uterus. Analysis on kinetics and Scatchard plot revealed the non-competitive type of the inhibition. In addition, arachidonate lowered dose-dependently the peak of labelled progestin or estrogen binding to the 8S receptor proteins, which were collected from fractions in the 8S region of the cytosols from intact or diethylstibestrol-primed rat uteri. These results suggest the generalized modulatory effect of arachidonate on the steroid hormone receptors in the central and peripheral tissues. Arachidonate could affect, negatively or positively, the estrogen receptors, and negatively the progestin, androgen and glucocorticoid receptors, through a possibly direct but weak binding at sites different from steroid binding sites on the receptor molecules. A potential messenger role of arachidonate itself has been implicated in the regulation or modulation of the steroid hormone receptors.     

The characteristic binding of catechol estrogens to estrogen receptors in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors

The binding of catechol estrogens (2-hydroxyestrone, 4-hydroxyestrone, 2-hydroxyestradiol, and 4-hydroxyestradiol) to estrogen receptors in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor cytosols was investigated. Cytosol estrogen receptors exhibited high affinities (Ka = 1.12-1.88 X 10(8) M-1) for all catechol estrogens as well as estradiol. The receptor level of catechol estrogens (46.1-97.5 fmol/mg protein) was 1.6-3.0 times higher than that of estradiol; especially the binding of 4-hydroxyestrone to estrogen receptors was the highest of all catechol estrogens and estradiol. In judging the receptor level of more than 20 fmol/mg protein to be positive, the binding of catechol estrogens to estrogen receptors was approximately correlated with that of estradiol. The positive receptor level of catechol estrogens was found in a half of tumor cytosols which showed the negative receptor level of estradiol. These results suggested that characteristic estrogen receptors indicating high affinities for catechol estrogens might be present in rat mammary tumor cytosols.     

The Impact of Androgen Receptor Expression on Breast Cancer Survival: A Retrospective Study and Meta-Analysis

Recent studies have highlighted the role of androgen receptor (AR) as a prognostic biomarker of breast cancer. However, its predictive role in disease free survival (DFS) and overall survival (OS) still remains inconclusive. The present study aimed to retrospectively investigate the association between AR and survival outcomes in breast cancer and also identify this association by a meta-analysis of published researches. Clinical data from 109 patients with breast cancer, who underwent surgery at Ruijin Hospital, Shanghai, were retrospectively analyzed for immunohistochemical AR expression measured by tissue microarray. For meta-analysis, articles available in Pubmed on the relationship between AR and breast cancer outcomes were included. Data obtained from both were combined and analyzed. Women with AR positive tumors in the retrospective study had a significantly better DFS (HR 0.24, 95% CI 0.07-0.88) and OS (HR 0.19, 95% CI 0.04-0.85) than women with AR negative ones. Meta-analysis showed that AR expression in breast tumors was an indicator of better DFS (HR 0.52, 95% CI 0.43-0.64). In subgroup analysis, AR could predict DFS outcome in estrogen receptor (ER) positive (HR 0.45, 95% CI 0.34-0.59), ER negative (HR 0.42, 95% CI 0.26-0.67), and triple negative breast cancer (HR 0.40, 95% CI 0.23-0.69). Moreover, in ER positive breast cancer patients, the expression of AR could predict better OS (HR 0.39, 95% CI 0.19-0.82). The present analysis indicated that AR expression was associated with lower risk of recurrence in patients with all breast cancer types and better OS in cases with ER positive.     

Biochemical and immunological characterization of estrogen binding components in human neoplastic adrenocortical tissues

The estrogen binding components in human adrenocortical tissues were examined. Two adrenocortical cancer cytosols were found to contain the binder with a relative low affinity (Kd 5 X 10(-9) M) for estradiol. The association of [3H]estradiol to these cytosols was inhibited by a large dose of unlabeled estrone, estradiol or estriol, but neither by diethylstilbestrol nor by dihydrotestosterone. Incubation of cultured cells derived from these cancers with [3H]estradiol also showed the presence of this low-affinity estradiol binder. The addition of bovine serum albumin into these cytosols surprisingly resulted in a marked increase in estradiol binding capacity in a concentration-dependent manner. This component sedimented at 5 S in the low salt sucrose density gradient. This binding ability was found to be heat-labile in the absence of estradiol, but preformation of complexes with estradiol markedly stabilized its binding ability against thermal inactivation. In addition, experiments using monoclonal antibodies to human estrogen receptor revealed that the estrogen binder from one adrenocortical cancer cytosol shared antigenic determinants with human estrogen receptor. These results suggest that the unique estrogen binder in some adrenocortical cancer has the characteristics similar to estrogen receptors in terms of thermal stability and immunological cross-reactivity to antibodies.     

Enhanced inhibition of estrogen receptor nuclear binding in the uterus of aged mice

We have studied why uteri from aging mice show a decrease nuclear concentration of estrogen receptors (UER). While 50-60% of available cytosolic UER from ovariectomized (OVX) mice aged 4-8 months, upon physiochemical activation, are able to bind either to DNA-cellulose or nuclear suspensions from young animals, only 20-30% of comparable concentrations of cytosolic UER from mice aged 15-18 months did so under identical experimental conditions. Nuclear dilutions with uterine cytosolic fractions from estrogen treated OVX mice prior to determination of [3H] UER binding sites in nuclear suspensions decreased the number of nuclear ER sites in both age groups. However, we observed that cytosols from aged animals showed a greater ability to prevent [3H]E2 binding to nuclear sites when compared to young ones (inhibition index: 0.286 +/- 0.013 (SE) vs. 0.137 +/- 0.025, P less than 0.05). These changes occur independently of protein concentration and result from dilution of a specific endogenous inhibitor of [3H]E2 binding to nuclear sites. The significance of these observed differences is discussed.     

Effects of steroid hormones on reproduction- and detoxification-related gene expression in adult male mosquitofish, Gambusia affinis

The molecular mechanisms that mediate fish reproduction and detoxification in response to steroid hormones were studied by using adult male western mosquitofish (Gambusia affinis) as sentinel species. The expression patterns of three vitellogenins (VtgA, VtgB and VtgC), two estrogen receptors (ERα and ERβ), two androgen receptors (ARα and ARβ), metallothionein (MT) and cytochrome P450 1A (CYP1A) in the liver and testis of adult male mosquitofish were assessed through exposure treatments with progesterone (P), testosterone (T) and 17β-estradiol (E2), alone and in combination for eight days. The results showed that expression patterns of Vtg subtype, ER subtype, AR subtype, MT and CYP1A genes in male mosquitofish varied according to tissue and specific hormone stress. Vtg subtype mRNA expression was induced in the liver in E2-added treatments, and an up-regulation of ERα mRNA expression was also observed. In addition, hormone treatments increased three Vtg subtype mRNA expression levels in the testis, at least to some extent. All hormone treatments significantly inhibited ERα, ERβ and ARβ mRNA expression in the testis. Some of hormone treatments could affect MT and CYP1A gene expression in mosquitofish. In general, multiple hormone treatments showed different effects on target gene expression compared with corresponding hormone alone. The results from the present study provided valuable information on the toxicological effects of steroid hormones in mosquitofish.     

Small molecule inhibitors as probes for estrogen and androgen receptor action

Because activated estrogen (ER) and androgen (AR) receptors stimulate cell proliferation in breast and prostate cancer, inhibiting their actions represents a major therapeutic goal. Most efforts to modulate ER and AR activity have focused on inhibiting the synthesis of estrogens or androgens or on the identification of small molecules that act by competing with agonist hormones for binding in the ligand-binding pocket of the receptor. An alternative approach is to implement screens for small molecule inhibitors that target other sites in the pathway of steroid receptor action. Many of these second-site inhibitors directly target ER or AR; others have still unknown sites of action. Small molecule inhibitors that target second sites represent new leads with clinical potential; they serve as novel modulators of receptor action; and they can reveal new and as yet unidentified interactions and pathways that modulate ER and AR action.     

Developmental changes in and hormonal regulation of estrogen and androgen receptors present in the rabbit epididymis

Both androgen and estrogen receptors (AR and ER) are present in the rabbit epididymis. We have used the sucrose gradient method to examine receptor sedimentation properties, receptor concentration, and distribution of receptors among the caput, corpus, and cauda of the epididymis to determine changes that occur in these parameters as the animals age. The 9S form of the ER is present in all three epididymal segments of the immature rabbit, with the highest concentration occurring in the cauda. The 8.2S form of the AR is also present in all three segments of the immature epididymis, with the highest concentration occurring in the caput. Short-term castration (3 days) leads to an increase in the amount of both AR and ER detected. ER are present in all segments of the immature epididymis at higher concentrations than AR. The functional 9S form of the ER disappears as the animals mature, the result of a tissue-specific protease that our laboratory previously has shown proteolyzes ER to a non-DNA-binding 3.8S form. Long-term castration (3 mo) of adult rabbits results in the reappearance of the 9S form of the ER in all segments of the epididymis. The reappearance of the 9S form of the ER is also seen in animals castrated for 1 mo, but not in those castrated for 2 wk. Administration of testosterone once daily for 2 wk to adult animals castrated for 6 wk results in the disappearance of the 9S form of the ER and the reappearance of the 3.8S form, suggesting that the tissue-specific protease is androgen-dependent. In this way, circulating androgens may play a role in regulating the concentration and form of the ER in the rabbit epididymis. There is little change in the concentration or distribution of AR in the epididymis of adult rabbits castrated for 3 mo as compared to those castrated for 3 days. This implies that circulating androgens are not required for maintenance of AR in the epididymis. Our data demonstrate that there are temporal differences in the presence and concentration of ER and AR in the epididymis and suggest that there is a differential, age-dependent regulation of the development and function of the epididymis by androgens and estrogens.     

Estrogen and androgen receptors in the liver of cynomolgus monkeys (Macaca fascicularis)

Estrogen receptors (ER) and androgen receptors (AR) were evaluated in the hepatic cytosol from cynomolgus macaques to determine if there were differences associated with gender and endogenous hormone secretion. Saturable, high affinity binding (Kd = 0.2-0.8 nM) was demonstrated for both ER and AR from either male or female monkeys. Displacement of tritiated estradiol from the ER was estrogen specific (including ethinyl estradiol). Both androgens and the synthetic progestins (levonorgestrel and norethindrone) displaced tritiated mibolerone from the AR. Both 8S and 4S molecular forms of ER and AR were demonstrated on 5-20% sucrose density gradients. The ER levels were higher in females in the follicular phase of the menstrual cycle (40.5 +/- 1.9 fmol/mg protein) than levels in males (26.4 +/- 4.8 fmol/mg protein; P less than 0.01) or levels in luteal phase females (31.8 +/- 2.4 fmol/mg protein; P less than 0.05). AR levels were not different between females during different phases of the menstrual cycle (65.8 +/- 4.6 and 69.5 +/- 4.3 fmol/mg protein, follicular and luteal, respectively), but there was a tendency (P less than 0.10) for the levels in males (54.4 +/- 6.6 fmol/mg protein) to be lower than female levels. The demonstration of saturable, high affinity binding of androgens and estrogens in liver tissue of these primates, along with differences associated with gender and the stage of the menstrual cycle, suggests that hepatic receptors are functional and may play an important role in hepatic protein secretion.